17 results on '"Moll I"'
Search Results
2. Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis.
- Author
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Gruber R, Börnchen C, Rose K, Daubmann A, Volksdorf T, Wladykowski E, Vidal-Y-Sy S, Peters EM, Danso M, Bouwstra JA, Hennies HC, Moll I, Schmuth M, and Brandner JM
- Subjects
- Adult, Down-Regulation, Female, Humans, Interleukin-13 genetics, Male, Skin metabolism, Skin pathology, Claudin-1 metabolism, Claudin-4 metabolism, Dermatitis, Atopic metabolism, Dermatitis, Atopic pathology, Keratinocytes pathology
- Abstract
Tight junctions are important for skin barrier function. The tight junction protein claudin 1 (Cldn-1) has been reported to be down-regulated in nonlesional skin of atopic dermatitis (AD) patients. In contrast, we did not observe a significant down-regulation of Cldn-1 in nonlesional skin of the AD cohort used in this study. However, for the first time, a significant down-regulation of Cldn-1 in the upper and lower epidermal layers of lesional skin was detected. In addition, there was a significant up-regulation of Cldn-4 in nonlesional, but not lesional, AD skin. For occludin, no significant alterations were observed. In an AD-like allergic dermatitis mouse model, Cldn-1 down-regulation in eczema was significantly influenced by dermal inflammation, and significantly correlated with hallmarks of eczema (ie, increased keratinocyte proliferation, altered keratinocyte differentiation, increased epidermal thickness, and impaired barrier function). In human epidermal equivalents, the addition of IL-4, IL-13, and IL-31 resulted in a down-regulation of Cldn-1, and Cldn1 knockdown in keratinocytes resulted in abnormal differentiation. In summary, we provide the first evidence that Cldn-1 and Cldn-4 are differentially involved in AD pathogenesis. Our data suggest a role of Cldn-1 in AD eczema formation triggered by inflammation., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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3. Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes.
- Author
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Kirschner N, Rosenthal R, Furuse M, Moll I, Fromm M, and Brandner JM
- Subjects
- Animals, Cells, Cultured, Claudin-1 deficiency, Claudin-1 genetics, Claudin-1 physiology, Claudin-4 deficiency, Claudin-4 genetics, Claudin-4 physiology, Keratinocytes cytology, Male, Mice, Mice, Knockout, Models, Animal, Occludin deficiency, Occludin genetics, Occludin physiology, Tight Junction Proteins deficiency, Tight Junction Proteins genetics, Zonula Occludens-1 Protein deficiency, Zonula Occludens-1 Protein genetics, Zonula Occludens-1 Protein physiology, Cell Membrane Permeability physiology, Ions metabolism, Keratinocytes metabolism, Macromolecular Substances metabolism, Tight Junction Proteins physiology, Tight Junctions physiology, Water metabolism
- Abstract
Tight junctions (TJs) form a selective barrier for ions, water, and macromolecules in simple epithelia. In keratinocytes and epidermis, TJs were shown to be involved in individual barrier functions. The absence of the TJ protein claudin-1 (Cldn1) in mice results in a skin-barrier defect characterized by lethal water loss. However, detailed molecular analyses of the various TJ barriers in keratinocytes and the contribution of distinct TJ proteins are missing. Herein, we discriminate TJ-dependent paracellular resistance from transcellular resistance in cultured keratinocytes using the two-path impedance spectroscopy. We demonstrate that keratinocyte TJs form a barrier for Na(+), Cl(-), and Ca(2+), and contribute to barrier function for water and larger molecules of different size. In addition, knockdown of Cldn1, Cldn4, occludin, and zonula occludens-1 increased paracellular permeabilities for ions and larger molecules, demonstrating that all of these TJ proteins contribute to barrier formation. Remarkably, Cldn1 and Cldn4 are not critical for TJ barrier function for water in submerged keratinocyte cultures. However, Cldn1 influences stratum corneum (SC) proteins important for SC water barrier function, and is crucial for TJ barrier formation for allergen-sized macromolecules.
- Published
- 2013
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4. Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
- Author
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Rachow S, Zorn-Kruppa M, Ohnemus U, Kirschner N, Vidal-y-Sy S, von den Driesch P, Börnchen C, Eberle J, Mildner M, Vettorazzi E, Rosenthal R, Moll I, and Brandner JM
- Subjects
- Adult, Aged, Aged, 80 and over, Calcium metabolism, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Adhesion radiation effects, Cell Differentiation radiation effects, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Claudins genetics, Claudins metabolism, Female, Homeostasis radiation effects, Humans, Keratinocytes cytology, Keratinocytes metabolism, Male, Middle Aged, Neoplasm Grading, Occludin antagonists & inhibitors, Occludin metabolism, RNA, Small Interfering genetics, Signal Transduction radiation effects, Skin Neoplasms metabolism, Skin Neoplasms pathology, Tight Junctions metabolism, Tight Junctions pathology, Tight Junctions radiation effects, Young Adult, Zonula Occludens-1 Protein genetics, Zonula Occludens-1 Protein metabolism, Carcinoma, Squamous Cell genetics, Cell Transformation, Neoplastic radiation effects, Epithelial-Mesenchymal Transition radiation effects, Gene Expression Regulation, Neoplastic radiation effects, Keratinocytes radiation effects, Occludin genetics, Skin Neoplasms genetics
- Abstract
Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.
- Published
- 2013
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5. Tight junctions and differentiation--a chicken or the egg question?
- Author
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Kirschner N, Rosenthal R, Günzel D, Moll I, and Brandner JM
- Subjects
- Animals, Humans, Mice, Skin metabolism, Cell Differentiation physiology, Keratinocytes cytology, Membrane Proteins metabolism, Tight Junctions metabolism
- Abstract
Skin barrier function is indispensable to prevent the uncontrolled loss of water and solutes and to protect the body from external assaults. To fulfil this function, keratinocytes undergo a complex pathway of differentiation that terminates in the formation of the stratum corneum. Additionally, tight junctions (TJs), which are cell-cell junctions localized in the stratum granulosum, are involved in the barrier function of the skin. Important biological and clinical roles of TJs are strongly suggested by altered TJ protein levels and distribution in skin diseases like psoriasis, ichthyosis and atopic dermatitis. Because these skin diseases show alterations in differentiation and TJs, it was suggested that changes in TJs might simply be a consequence of altered differentiation. However, in this viewpoint, we like to argue that the situation is not as simple and depends on the specific microenvironment. We discuss three hypotheses regarding the interplay between TJs/TJ proteins and differentiation: (1) TJs/TJ proteins are influenced by differentiation, (2) differentiation is influenced by TJs/TJ proteins, and (3) TJs/TJ proteins and differentiation are independent of each other. In addition, the concept is introduced that both processes are going on at the same time, which means that while one specific TJ protein/barrier component might be influenced by differentiation, the other may influence differentiation., (© 2011 John Wiley & Sons A/S.)
- Published
- 2012
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6. Intercellular adhering junctions with an asymmetric molecular composition: desmosomes connecting Merkel cells and keratinocytes.
- Author
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Rickelt S, Moll I, and Franke WW
- Subjects
- Animals, Cattle, Female, Humans, Mice, Rats, Swine, Adherens Junctions metabolism, Adherens Junctions ultrastructure, Desmosomes metabolism, Desmosomes ultrastructure, Keratinocytes metabolism, Keratinocytes ultrastructure, Merkel Cells metabolism, Merkel Cells ultrastructure, Plakophilins metabolism
- Abstract
Merkel cells (MCs) are special neuroendocrine epithelial cells that occur as individual cells or as cell groups within the confinements of a major epithelium formed and dominated by other epithelial cells. In the epidermis and some of its appendages MCs are mostly located in the basal cell layer, occasionally also in suprabasal layers and generally occur in linear arrays in outer root sheath cell layers of hair follicles. As MCs are connected to the adjacent keratinocytes by a series of adhering junctions (AJs), of which the desmosomes are the most prominent, these junctions represent heterotypic cell-cell connections, i.e. a kind of structure not yet elucidated in molecular terms. Therefore, we have studied these AJs in order to examine the molecular composition of the desmosomal halves. Using light- and electron-microscopic immunolocalization and keratin 20 as the MC-specific cell type marker we show that the plaques of the MC half of the desmosomes specifically and constitutively contain plakophilin Pkp2. This protein, however, is absent in the keratinocyte half of such heterotypic desmosomes which instead contains Pkp1 and/or Pkp3. We discuss the developmental, tissue-architectonic and functional importance of such asymmetric junctions in normal physiology as well as in diseases, in particular in the formation of distant tumor cell metastasis.
- Published
- 2011
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7. CD44 regulates tight-junction assembly and barrier function.
- Author
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Kirschner N, Haftek M, Niessen CM, Behne MJ, Furuse M, Moll I, and Brandner JM
- Subjects
- Adaptor Proteins, Signal Transducing, Adjuvants, Immunologic metabolism, Adjuvants, Immunologic pharmacology, Animals, Cell Adhesion Molecules metabolism, Cell Cycle Proteins, Cell Differentiation physiology, Cell Polarity physiology, Cells, Cultured, Female, Gene Expression physiology, Guanine Nucleotide Exchange Factors metabolism, Hyaluronan Receptors genetics, Hyaluronic Acid metabolism, Hyaluronic Acid pharmacology, Male, Mice, Mice, Knockout, Neuropeptides metabolism, Permeability drug effects, Phenotype, T-Lymphoma Invasion and Metastasis-inducing Protein 1, Tight Junctions drug effects, rac GTP-Binding Proteins metabolism, rac1 GTP-Binding Protein, Epidermal Cells, Epidermis metabolism, Hyaluronan Receptors metabolism, Keratinocytes cytology, Keratinocytes metabolism, Tight Junctions metabolism
- Abstract
Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and associated cell polarity complexes, which in turn contributes to altered skin barrier function in CD44 KO mice. We show a delay in embryonic barrier formation associated with a loss of apical LB localization in CD44 KO mice, which correlates with alterations in TJ proteins and Par3. Simultaneously, the activity of Rac1, a major regulator of TJ barrier function, was reduced. Importantly, normalization of barrier function at E18.5 coincided with the recovery of these proteins. Tape-stripping experiments revealed that the loss of CD44 also affected TJ proteins upon induced disturbance of the barrier in adult mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were impaired. An alteration of differentiation markers was also observed, but was less pronounced than alterations of TJ proteins. Taken together, the results reveal an important function for CD44 in the assembly and function of TJs, suggesting their involvement in the skin barrier phenotype of CD44 KO mice.
- Published
- 2011
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8. Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines.
- Author
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Kirschner N, Poetzl C, von den Driesch P, Wladykowski E, Moll I, Behne MJ, and Brandner JM
- Subjects
- Cells, Cultured, Claudin-1, Claudin-4, Claudins, Disease Progression, Down-Regulation, Humans, Interleukin-1beta pharmacology, Keratinocytes ultrastructure, Membrane Proteins biosynthesis, Occludin, Phosphoproteins biosynthesis, Psoriasis pathology, Tumor Necrosis Factor-alpha pharmacology, Up-Regulation drug effects, Zonula Occludens-1 Protein, Keratinocytes metabolism, Psoriasis metabolism, Tight Junctions metabolism
- Abstract
Psoriasis is an inflammatory skin disease characterized by hyperproliferation of keratinocytes, impaired barrier function, and pronounced infiltration of inflammatory cells. Tight junctions (TJs) are cell-cell junctions that form paracellular barriers for solutes and inflammatory cells. Altered localization of TJ proteins in the epidermis was described in plaque-type psoriasis. Here we show that localization of TJ proteins is already altered in early-stage psoriasis. Occludin, ZO-1, and claudin-4 are found in more layers than in normal epidermis, and claudin-1 and -7 are down-regulated in the basal and in the uppermost layers. In plaque-type psoriasis, the staining patterns of occludin and ZO-1 do not change, whereas the claudins are further down-regulated. Near transmigrating granulocytes, all TJ proteins except for junctional adhesion molecule-A are down-regulated. Treatment of cultured keratinocytes with interleukin-1beta and tumor necrosis factor-alpha, which are present at elevated levels in psoriatic skin, results in an increase of transepithelial resistance at early time points and a decrease at later time points. Injection of interleukin-1beta into an ex vivo skin model leads to an up-regulation of occludin and ZO-1, resembling TJ protein alteration in early psoriasis. Our results show for the first time that alteration of TJ proteins is an early event in psoriasis and is not the consequence of the more profound changes found in plaque-type psoriasis. Our data indicate that cytokines are involved in alterations of TJ proteins observed in psoriasis.
- Published
- 2009
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9. Expression of matrix metalloproteinases, cytokines, and connexins in diabetic and nondiabetic human keratinocytes before and after transplantation into an ex vivo wound-healing model.
- Author
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Brandner JM, Zacheja S, Houdek P, Moll I, and Lobmann R
- Subjects
- Adult, Aged, Biopsy, Cell Culture Techniques, Connexin 26, DNA Primers, Diabetes Mellitus enzymology, Diabetes Mellitus pathology, Female, Humans, Keratinocytes cytology, Keratinocytes pathology, Male, Middle Aged, Polymerase Chain Reaction, RNA genetics, RNA isolation & purification, Reference Values, Connexins genetics, Cytokines genetics, Diabetes Mellitus genetics, Keratinocytes physiology, Matrix Metalloproteinases genetics
- Abstract
Objective: Wound healing is known to require a well-organized balance of numerous factors, e.g., cytokines, matrix metalloproteinases (MMPs), and their inhibitors, as well as direct cell-cell communication (connexins). Disruption of this balance may lead to the formation of chronic wounds such as diabetic foot ulcers. The transplantation of autologous keratinocytes is a promising therapy for diabetic foot ulcers; however, little is known about their characteristics on a molecular level. Therefore, we intended to characterize transplanted keratinocytes from diabetic and nondiabetic origin before and after transplantation., Research Design and Methods: We isolated human keratinocytes from diabetic and nondiabetic origins and transplanted them into an ex vivo wound healing model. To characterize the keratinocytes, we investigated mRNA expression of MMP-1, MMP-2, and MMP-9; tissue inhibitor of MMP (TIMP)-1 and TIMP-2; interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha; Cx26 (connexin 26) and Cx43; and, for connexins, immunolocalization., Results: We found no significantly increased expression of the molecules investigated in cultured keratinocytes from diabetic compared with nondiabetic origin, even though there were significant differences for MMP-2, IL-1beta, and TNF-alpha in skin biopsies. Expression of IL-1beta was significantly lower in keratinocytes from diabetic origin. In the course of wound healing, differences in the dynamics of expression of MMP-1, IL-1beta, and Cx43 were observed., Conclusions: Our results suggest that keratinocytes from diabetic origin are as capable for transplantation into chronic wounds as keratinocytes from healthy origin at the starting point of therapy. However, differences in expression dynamics later on might reflect the systemic influence of diabetes resulting in a memory of the transplanted keratinocytes.
- Published
- 2008
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10. Organization and formation of the tight junction system in human epidermis and cultured keratinocytes.
- Author
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Brandner JM, Kief S, Grund C, Rendl M, Houdek P, Kuhn C, Tschachler E, Franke WW, and Moll I
- Subjects
- Calcium metabolism, Cells, Cultured, Claudin-1, Epidermis metabolism, Female, Fetus, Humans, Immunohistochemistry, Keratinocytes metabolism, Membrane Proteins genetics, Membrane Proteins metabolism, Occludin, Phosphoproteins genetics, Phosphoproteins metabolism, Pregnancy, Tight Junctions ultrastructure, Zonula Occludens-1 Protein, Cell Adhesion, Epidermis ultrastructure, Keratinocytes ultrastructure, Tight Junctions metabolism
- Abstract
Occludin and several proteins of the claudin family have been identiried in simple epithelia and in endothelia as major and structure-determining transmembrane proteins clustered in the barrier-forming tight junctions (TJ), where they are associated with a variety of TJ plaque proteins, including protein ZO-1. To examine whether TJ also occur in the squamous stratified epithelium of the interfollicular human epidermis we have applied several microscopic and biochemical techniques. Using RT-PCR techniques, we have identiried mRNAs encoding protein ZO-1, occludin and claudins 1, 4, 7, 8, 11, 12, and 17 in both tissues, skin and cultured keratinocytes, whereas claudins i and 10 have only been detected in skin tissue. By immunocytochemistry we have localized claudin-1, occludin and protein ZO-1 in distinct plasma membrane structures representing cell-cell attachment zones. While claudin-1 occurs in plasma membranes of all living cell layers, protein ZO-1 is concentrated in or even restricted to the uppermost layers, and occludin is often detected only in the stratum granulosum. Using electron microscopy, typical TJ structures ("kissing points") as well as some other apparently related junctional structures have been detected in the stratum granulosum, interspersed between desmosomes. Modes and patterns of TJ formation have also been studied in experimental model systems, e.g., during wound healing and stratification as well as in keratinocyte cultures during Ca2+-induced stratification. We conclude that the epidermis contains in the stratum granulosum a continuous zonula occludens-equivalent structure with typical TJ morphology and molecular composition, characterized by colocalization of occludin, claudins and TJ plaque proteins. In addition, cell-cell contact structures and certain TJ proteins can also be detected in other epidermal cell layers in specific cell contacts. The pattern of formation and possible functions of epidermal TJ and related structures are discussed.
- Published
- 2002
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11. Characterization of epidermal wound healing in a human skin organ culture model: acceleration by transplanted keratinocytes.
- Author
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Moll I, Houdek P, Schmidt H, and Moll R
- Subjects
- Adolescent, Adult, Cell Division, Female, Humans, Keratinocytes transplantation, Keratins analysis, Male, Middle Aged, Organ Culture Techniques, Regeneration, Epidermis physiology, Keratinocytes physiology, Wound Healing
- Abstract
Few data are available on early regeneration of human epidermis in vivo. We have established a supravital skin organ culture model for epidermal wound healing by setting a central defect (3 mm diameter) in freshly excised skin specimens and culturing under air exposure. Re-epithelialization was followed for up to 7 d by histology and immunohistologic analysis of various markers for differentiation and proliferation. In 12 of 19 cases (63%; 5% fetal calf serum) or six of 21 cases (29%; 2% fetal calf serum), the wounds were re-epithelialized spontaneously after 7 d. After transplantation to the wounds of 1-2 x 10(6) dissociated allogenic cultured epidermal or about 1 x 10(6) autologous outer root sheath keratinocytes, 18 of 21 cases (86%; 5% fetal calf serum) or 17 of 21 cases (81%; 2% fetal calf serum) were healed within the same period. Histologically, early neoepithelium (3 d) was disordered after keratinocyte transplantation, whereas later (7 d) it had gained a more ordered stratification, exhibiting a thin discontinuous granular and a compact horny layer. At this stage, not only hyperproliferative (CK 6) but also, abundantly, maturation-associated cytokeratins (CK 1, CK 10) were detected immunohistochemically. Analyses of regenerated epidermis after transplantation of (i) keratinocytes labeled in vitro with BrdU and (ii) heterosexual keratinocytes by immunohistochemistry and fluorescence in situ hybridization for the Y chromosome, respectively, clearly showed that external keratinocytes are physically integrated into the regenerated epidermis and extendedly contribute to its formation. The data presented here demonstrate improvement and acceleration of epidermal re-epithelialization by transplantation of keratinocytes.
- Published
- 1998
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12. [Use of keratinocytes in therapy of ulcera crurum].
- Author
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Moll I, Schönfeld M, and Jung EG
- Subjects
- Adult, Aged, Aged, 80 and over, Cells, Cultured, Female, Follow-Up Studies, Humans, Leg Ulcer etiology, Male, Middle Aged, Treatment Outcome, Varicose Ulcer etiology, Wound Healing physiology, Keratinocytes transplantation, Leg Ulcer therapy, Varicose Ulcer therapy
- Abstract
Freshly isolated keratinocytes were used for the treatment of non-healing leg ulcers (21 cases). For application, keratinocytes were suspended in fibrin (Tissucol Duo S). One or more applications of keratinocytes initiated granulation and reepithelialization of nearly all leg ulcers (20 cases). The method is compared with the established therapy entailing transplantation of allogenic keratinocyte sheets onto leg ulcers. Our method shows the advantages: autologous cells that are immediately and easily available, freedom from pain, and short-time immobilization (48 h) after application.
- Published
- 1995
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13. Proliferative potential of different keratinocytes of plucked human hair follicles.
- Author
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Moll I
- Subjects
- Cell Division, Cells, Cultured, Dissection, Filaggrin Proteins, Humans, Integrin beta1, Integrins analysis, Keratinocytes chemistry, Keratins analysis, Hair cytology, Keratinocytes cytology
- Abstract
We have examined colony-forming ability, localization of colony-forming cells, and in vitro life spans of outer root sheath keratinocytes of different fragments of adult human plucked hair follicles. These were shown by immunohistochemical staining for cytokeratins and integrins to contain a preserved basal cell layer. By microdissection, five fragments of the outer root sheath (B1, B2, B3-1, B3-2, B4) were separated, dispersed by trypsin into single cell suspensions, and grown on human feeder fibroblasts. All fragments gave rise to at least some colonies, but colony-forming ability was mostly marked in the intermediate part (B2) and the lower half of the central part (B3-1); approximately 60% of colony-forming cells of a hair follicle localized to the fragment B3-1 and 28% to the fragment B3-2 (upper half of the central part, including bulge). To compare the in vitro life spans of cells from the various fragments, we subcultured isolated keratinocytes under identical conditions. The longest was found in the fragment B3-2 and the shortest in the fragment B1 (bulb). Moreover, the differentiation state of the native cells and the cells of all cultures were studied during their whole life spans by immunocytochemical analysis of various proliferation and differentiation markers. Surprisingly, keratinocytes of all fragments, as shown by expression of high-molecular-weight cytokeratins and filaggrin, were capable of terminal differentiation. These data indicate that cells with long life spans are localized in central parts of the outer root sheath close to the bulge area and that cells with high colony-forming ability are localized in the lower central parts. The latter are usually removed by plucking and may therefore not represent stem cells but rather cells important for hair growth during a single cycle. Cells with long life spans--also included in plucked hair follicles--may be immediate progeny of stem cells that will be segregated in the bulge area. Finally, our results are important for gene transfer and stem cell gene therapy in genodermatoses, because plucked hair follicles are easily available and keratinocytes close to the bulge area should be used selectively.
- Published
- 1995
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14. [Keratinocytes from cell culture for therapy of skin defects. Review and personal results].
- Author
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Schönfeld M, Moll I, Maier K, and Jung EG
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Survival physiology, Cells, Cultured, Culture Techniques, Female, Humans, Male, Middle Aged, Keratinocytes transplantation, Pressure Ulcer surgery, Skin Transplantation methods, Varicose Ulcer surgery
- Abstract
The development of a method to cultivate and expand human keratinocytes in vitro by Rheinwald and Green in the mid-1970s can be considered a milestone in the search for the ideal biological skin substitute. For more than 10 years, cultured keratinocytes have now been used for the treatment of various wounds. In this paper the present status knowledge and the authors own experience after treating 29 patients are discussed.
- Published
- 1993
15. Keratinocyte carcinogenesis: introduction.
- Author
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Moll I
- Subjects
- Animals, Cell Division, Humans, Keratinocytes pathology, Keratinocytes physiology, Skin Neoplasms etiology
- Published
- 1993
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16. Special program of differentiation expressed in keratinocytes of human haarscheiben: an analysis of individual cytokeratin polypeptides.
- Author
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Moll I, Troyanovsky SM, and Moll R
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Differentiation, Electrophoresis, Gel, Two-Dimensional, Epidermal Cells, Epidermis metabolism, Hair, Humans, Immunohistochemistry, Keratinocytes metabolism, Middle Aged, Skin metabolism, Keratinocytes cytology, Keratins metabolism, Peptides metabolism, Skin cytology
- Abstract
Human haarscheiben, epidermal Merkel cell-rich sensory organs of hairy skin, were studied for the expression of various cytokeratin (CK) polypeptides and other epithelial and neuronal differentiation markers by applying immunoperoxidase and immunofluorescence microscopy to frozen sections and by two-dimensional gel electrophoresis. The basal clusters of Merkel cells were specifically detected by antibodies against CK 20. Haarscheiben keratinocytes were unique mainly by the prominent expression of CK 17 in the lower and middle layers. Further differences as compared to keratinocytes of usual epidermis included the enlargement of the basal compartment, characterized by the expression of CK 5 and the absence of the maturation-associated CKs 1/10/11, and the reduction of CK 15, which is a constituent of normal basal cells. Using CK 17 as a highly sensitive Haarscheibe marker in skin tissue sections, variabilities in the spatial relationship of the haarscheibe and the corresponding hair follicle were recorded. The results show that haarscheibe keratinocytes express a special program of differentiation that may be important for optimal stimulus perception. Immunohistochemical stainings for CK 17 will facilitate further studies on the distribution and biology of haarscheibe.
- Published
- 1993
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17. Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment.
- Author
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Haass, Nikolas K., Ripperger, D., Wladykowski, E., Dawson, P., Gimotty, P. A., Blome, C., Fischer, F., Schmage, P., Moll, I., and Brandner, Johanna M.
- Subjects
MELANOMA ,FIBROBLASTS ,KERATINOCYTES ,GAP junctions (Cell biology) ,SKIN cancer - Abstract
Melanoma depends on, interacts with and reacts to the stroma in which it is embedded, including fibroblasts, extracellular matrix, endothelial cells and immune cells. However, the impact of melanoma on the epidermal tumor microenvironment—the multilayered epithelium of the skin—is poorly understood. Gap junctions are essential for intercellular communication and involved in proliferation, differentiation and homeostasis of keratinocytes. We have shown previously that the gap junction proteins connexin 26 and 30 (Cx26 and Cx30) are induced in the epidermal tumor microenvironment of skin cancers including melanoma. This study compares the extent of Cx26, Cx30 and Cx43 expression in the epidermal microenvironment of melanocytic nevi and melanomas and its association with melanoma thickness, proliferative index of the tumor and its microenvironment, and with 5-year metastasis and survival. We found that induction of Cx26 and Cx30 cell–cell border expression in the epidermal tumor microenvironment correlates to malignancy. Importantly, there was a significant correlation of tumor thickness with the vertical epidermal Cx26 and Cx30 expression pattern and the horizontal Cx26 dissemination. Furthermore, horizontal Cx26 expression correlated with metastasis. Vertical epidermal expression patterns of Cx26 and Cx30 significantly correlated with the proliferative index in the epidermal tumor microenvironment but not with the proliferative index in the tumor. In contrast, Cx43 did not correlate with malignancy, thickness or proliferative index. In summary, here we show for the first time a significant association between the progression of melanoma and alterations in its epithelial tumor microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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