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Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disorder. Recently, it has been reported that dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with the development of BP (DPP4i-BP). Patients with DPP4i-BP have autoantibodies (autoAbs) preferentially targeting full-length BP180, but not the BP180NC16a domain. In this report, we described a case of anti-BP230 antibody (Ab)-positive BP receiving DPP4i. A 78-year-old male with a medical history of type 2 diabetes receiving vildagliptin at 100 mg daily for 38 months was referred to our hospital with itching blisters on his body and extremities. Skin biopsy showed subepidermal bulla with eosinophil infiltration. Direct immunofluorescence staining revealed a linear staining pattern with complement C3 and IgG at the subepidermal basement membrane zone. By laboratory testing, autoAbs against BP180NC16a and full-length BP180 were negative by enzyme-linked immunosorbent assay (ELISA); however, anti-BP230 Abs were positive by ELISA (index: 123.91). His HLA genotype was DQB1*04:01 and 05:01. Based on these results, we diagnosed the patient with anti-BP230 Abs-positive BP associated with DPP4i. To the best of our knowledge, this is the first case of DPP4i-BP with only anti-BP230 Abs. Further accumulation of DPP4i-BP cases is needed to clarify the relationship between overall features of DPP4i-BP and anti-BP230 Abs.

Erythropoietic protoporphyria is a genetic disease characterized by sensitivity to sunlight caused by the accumulation of protoporphyrin IX. Photoprotection against ultraviolet A and visible light is necessary for erythropoietic porphyria patients because the absorption spectrum of protoporphyrin IX lies in both ultraviolet A and visible light region. We developed a novel index, in vitro porphyrin protection factor, based on the protoporphyrin IX absorbance spectrum. We also selected appropriate photoprotective products designed according to protoporphyrin IX absorbance. The porphyrin protection factors of a combination of make‐up base with a powder as well as with a liquid foundation were significantly higher than those of a conventional sunscreen product, even at a small application dose. An in‐use test carried out for 6 months showed that the efficacy of these products was 78.3%, and no adverse reactions were observed. Male subjects preferred liquid foundation, whereas all female subjects used powder foundation. The preference of the subjects could lead to the long‐term use of the tested products. In conclusion, this study provided a new approach to improve photoprotection in erythropoietic protoporphyria patients.

A topical application of a nonsteroidal anti-inflammatory drug (NSAID) may induct an adverse reaction of photoallergic contact dermatitis. The occlusive usage may provoke concomitant photoallergic sensitizations to an NSAID and other ingredients. We describe a 58-year-old woman with photoallergic contact dermatitis from ketoprofen and hydrogenated rosin glycerol ester in the applied compress. Our case indicates that photopatch testing with all ingredients is required to verify the actual photoallergen(s).

Amelanotic vulvar melanoma is a rare type of malignant melanoma. This paper describes a case of an asymptomatic ulcerated nodule 20 mm in size. The tumor cells from the nodular lesion showed positive staining immunohistochemically for Melan-A, but negative staining with HMB-45. The cells showed negative reactivity to S-100 except in one region. The melanoma cells in the epidermis were detected in one of the specimens from the excised tumor nodule. The cells in the epidermis showed positive staining for Melan-A and S-100 and partial staining with HMB-45. The tumor was diagnosed as malignant melanoma of the vulva and immunohistochemically shown to have intratumor histological heterogeneity. This case suggests the importance of viewing non-pigmented nodules on the vulva of elderly females as potentially malignant melanoma, and that a combination of immunohistochemical stains may be useful for recognizing the stage of the melanosomes in the melanoma cells.

Lichen amyloidosus (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Clinical regression is usually difficult to achieve, even after treatment. In this study, we report a case of an adult man with LA associated with atopic dermatitis (AD) which was successfully treated with narrowband ultraviolet B (NB-UVB) phototherapy, topical corticosteroids and an oral antihistamine. This case suggests that NB-UVB phototherapy may be a useful adjuvant for LA associated with AD.

Retinol is known to be effective in the treatment of sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti-wrinkle effects of a new cosmetic containing retinol. An open study was performed in 30 healthy Japanese women who had wrinkles at the corners of the eyes. The tested lotion, Retin-OX+ (RoC SA, Colombes, France), was applied on wrinkles of one side of the face for 8 weeks, and not on the other site as a control. Anti-wrinkle effects were evaluated by two methods: (i) doctors' observation and photos based on the guideline of the Japan Cosmetic Industry Association; and (ii) the Robo Skin Analyzer. This lotion showed marked and moderate improvement in 34% of the subjects with a significant difference as compared with the control sites (P < 0.05). Moreover, the length and area decreased in the applied site more than the control site with a significant difference (P < 0.01). All the patients completed the study without significant adverse reactions. The tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles at the corner of the eyes.

Niacinamide is known to have effectiveness on sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti-wrinkle effects of a new cosmetic containing niacinamide. A randomized, placebo-controlled, split face study was performed in 30 healthy Japanese females who had wrinkles in the eye areas. The tested cosmetic containing 4% niacinamide was applied on wrinkles of one side for 8 weeks, and a control cosmetic without niacinamide on another site. Anti-wrinkle effects were evaluated with two methods: (i) doctors' observation and photographs based on the guideline of the Japan Cosmetic Industry Association; and (ii) average roughness of skin surface (Ra value) using skin replica. This cosmetic showed marked and moderate improvement in 64% of the subjects with a significant difference as compared with the control site (P < 0.001). Wrinkle grades in the tested area significantly reduced more than pre-application (P < 0.001) and the control (P < 0.001). Reduction in Ra value on the tested area was more than pre-application (P < 0.01) and the control site (P < 0.05) with significant differences. Only one subject stopped the study with minimal irritation. These results indicated that the tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles in the eye areas.

The purpose of this study was to investigate the efficacy of phototherapy with a newly-developed 1450-nm diode laser in patients with mild to moderate acne. An open study was performed in acne patients who were treated up to five times with a two week interval. Acne lesions were reduced by 63%. Only one patient discontinued treatment due to vesicle formation as an adverse effect. Phototherapy using this diode laser source was effective and well tolerated in acne patients, suggesting that this phototherapy may be a new modality for the treatment of acne.

Summary Psoriasis is believed to be a T cell-mediated autoimmune disease, but also exhibits autoantibody production. Calpastatin is an endogenous inhibitor of calpain, a ubiquitous protease that regulates inflammatory processes. Anti-calpastatin autoantibody was first identified as an autoantibody specific to rheumatoid arthritis, but has been also detected in other autoimmune diseases. In this study, we examined the presence and levels of anti-calpastatin antibody in 77 psoriasis patients by enzyme-linked immunosorbent assay. Compared with normal controls, psoriasis patients exhibited significantly elevated IgG anti-calpastatin antibody levels that were similar to those found in rheumatoid arthritis patients. Remarkably, IgG anti-calpastatin autoantibody in sera from psoriasis patients inhibited calpastatin activity. Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis.

Hapten sensitization through UV-exposed skin induces systemic immune suppression, which is experimentally demonstrated by inhibition of contact hypersensitivity (CHS). Although this UV-induced effect has been shown to be mediated by inhibition of the afferent phase of the CHS, the UV effects on the efferent (elicitation) phase remain unknown. In this study, UV effects on endothelial ICAM-1 expression at elicitation sites were first examined. Mice were sensitized by hapten application onto UV-exposed back skin, and ears were challenged 5 days later. ICAM-1 up-regulation at nonirradiated elicitation sites following hapten challenge was eliminated by UV exposure on sensitization sites distant from elicitation sites. To assess whether loss of the ICAM-1 up-regulation at elicitation sites contributed to UV-induced immunosuppression, we examined CHS responses in UV-exposed ICAM-1-deficient (ICAM-1−/−) mice that genetically lacked the ICAM-1 up-regulation. ICAM-1−/− mice exhibited reduced CHS responses without UV exposure, but UV exposure did not further reduce CHS responses in ICAM-1−/− mice. Furthermore, ICAM-1 deficiency did not affect the afferent limb, because ICAM-1−/− mice had normal generation of hapten-specific suppressor and effector T cells. This UV-induced immunosuppression was associated with a lack of TNF-α production after Ag challenge at elicitation sites. Local TNF-α injection before elicitation abrogated the UV-induced CHS inhibition with increased endothelial ICAM-1 expression. TNF-α production at elicitation sites was down-regulated by IL-10, a possible mediator produced by hapten-specific suppressor T cells that are generated by UV exposure. These results indicate that UV exposure inhibits CHS by abrogating up-regulation of endothelial ICAM-1 expression after Ag challenge at elicitation sites.

Infantile hemangioma precursors or those without a proliferative phase may mimic a port-wine stain. We describe a case of infantile hemangioma precursor, which proved to be Glut-1 positive in biopsy, with the dermoscopic features of red round globular vessels, red comma-like vessels, and red linear vessels. These dermoscopic features should help to distinguish infantile hemangioma precursors or those with an absent or minimal growth phase from a port-wine stain.

妊娠による悪化を来した汎発性膿疱性乾癬(GPP)患者の治療経過を報告した。妊娠初期および中期の膿疱化にはシクロスポリンA(Cy-A)2～4mg/kg/日の内服が有効であった。しかし,妊娠後期の膿疱化にはCy-A 5.5mg/kg/日の大量投与もプレドニゾロン40mg/日とCy-A 4mg/kg/日の併用も無効であり,高度の発熱と全身状態の悪化を認めたため,妊娠31週で帝王切開を行い児を娩出した。児は出生時体重1672gで新生児ICUでの全身管理を要したが,以後順調に発育し退院した。患者に対しては分娩の翌日からエトレチナート50mg/日の投与に変更したところ,臨床症状の劇的な改善をみた。Cy-Aは妊娠に伴うGPPの治療に使用可能な薬剤のひとつと思われるが,子宮内胎児発育遅滞や催奇性のリスクが低いながら存在するので,その使用に際しては十分な説明を行い患者の同意を得る必要がある。

Disseminated superficial actinic porokeratosis (DSAP) is a subtype of porokeratosis, thought to be clonal disorder of keratinization. Chronic exposure to ultraviolet (UV) light might be an etiological cause of DSAP, of which frequent sites are sun-exposed areas. We report a case of DSAP that occurred on the trunk of a 79-year-old man with psoriasis treated with narrowband ultraviolet B (NB-UVB) for clearing and maintenance therapies. DSAP has been reported to associate with psoralen and ultraviolet A therapy and broadband UVB, but not NB-UVB. This may be the first case of DSAP after repeated exposure to NB-UVB.

SUMMARYL-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI ≥ 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.

Skin fibrotic disorders are understood to develop under the influence of some growth factors, such as transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), or connective tissue growth factor (CTGF). To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of growth factors by injecting TGF-beta, CTGF, and bFGF into the subcutaneous tissue of newborn mice. A single application of TGF-beta or bFGF resulted in the formation of transient granulated tissue that disappeared despite 7 days of consecutive injections. A single CTGF injection also caused slight granulation. However, injecting TGF-beta plus CTGF produced long-term fibrotic tissue, which persisted for at least 14 days. Also, fibrotic tissue was observed when CTGF was injected from 4 to 7 days after TGF-beta injections for the first 1-3 days. In situ hybridization analysis revealed the expression of CTGF mRNA in the fibroblasts at least in a few fibrotic conditions. These findings suggest that either CTGF mRNA or an application of exogenous CTGF protein is required for the development of persistent fibrosis. From our study, it appears that interaction of several growth factors is required for persistent fibrotic tissue formation, with TGF-beta causing the induction and CTGF needed for maintenance of skin fibrosis. The animal model on skin fibrosis by exogenous application of growth factors developed in this study may prove useful for future studies on fibrotic disorders.

To detect DNA aneuploidy in Bowen’s disease, we investigated DNA flow cytometric analysis. Single cell suspensions were prepared from 18 fresh samples histopathologically diagnosed as solitary Bowen’s disease and analyzed by DNA flow cytometry. In 16 (89%) of 18 lesions, DNA aneuploidy was demonstrated with a single aneuploid peak. DNA indices ranged from 1.29 to 1.74. The incidence of DNA aneuploidy in Bowen’s disease is higher than those of cutaneous squamous cell carcinoma, which was 25–80% in the previous reports. Therefore, in Bowen’s disease, DNA aneuploidy may not imply a good marker for characteristics of non-melanoma skin cancer. A single aneuploid peak commonly observed in Bowen’s disease suggests that this disease consists of the monoclonal proliferation of keratinocytes containing abnormal DNA content.

Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients. We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association.

Disseminated superficial actinic porokeratosis (DSAP) is a subtype of porokeratosis, thought to be clonal disorder of keratinization. Chronic exposure to ultraviolet (UV) light might be an etiological cause of DSAP, of which frequent sites are sun-exposed areas. We report a case of DSAP that occurred on the trunk of a 79-year-old man with psoriasis treated with narrowband ultraviolet B (NB-UVB) for clearing and maintenance therapies. DSAP has been reported to associate with psoralen and ultraviolet A therapy and broadband UVB, but not NB-UVB. This may be the first case of DSAP after repeated exposure to NB-UVB.

Infantile hemangioma precursors or those without a proliferative phase may mimic a port-wine stain. We describe a case of infantile hemangioma precursor, which proved to be Glut-1 positive in biopsy, with the dermoscopic features of red round globular vessels, red comma-like vessels, and red linear vessels. These dermoscopic features should help to distinguish infantile hemangioma precursors or those with an absent or minimal growth phase from a port-wine stain.

Follicular mucinosis (alopecia mucinosa) is often associated with malignancies including mycosis fungoides and Sezary syndrome, but not adult T-cell leukemia-lymphoma (ATLL). We report a 49-year-old male patient who had pruritic follicular papules and erythemas clinically, and follicular and perifollicular infiltrates and follicular mucin deposition histopathologically. The patient showed 11% of flower-shaped atypical lymphocytes in blood examination and positive human T-cell leukemia virus type 1 antibody in serology, consistent with the chronic type of ATLL. This case seems to be a very rare association of follicular mucinosis and chronic ATLL, suggesting that malignant T cells may have a feature of folliculotropism as well as epidermotropism.

Pityriasis rubra pilaris (PRP) is a papulosquamous disorder comprising 6 clinical types. Some factors – including abnormal vitamin A metabolism, internal malignancies, autoimmune diseases, infection and trauma – are thought to be involved in the etiology. Recently, human immunodeficiency virus (HIV)-associated PRP has been reported to have distinct clinical features, such as nodulocystic acne and lichen spinulosus alongside PRP. We report here the case of a 38-year-old female with onset of classical PRP after a high fever. Virological studies indicated that the patient had primary systemic cytomegalovirus (CMV) infection and not HIV infection. Our case suggested that primary CMV infection might have triggered typical PRP that was clinically different from HIV-associated PRP.

Niacinamide is known to have effectiveness on sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti-wrinkle effects of a new cosmetic containing niacinamide. A randomized, placebo-controlled, split face study was performed in 30 healthy Japanese females who had wrinkles in the eye areas. The tested cosmetic containing 4% niacinamide was applied on wrinkles of one side for 8 weeks, and a control cosmetic without niacinamide on another site. Anti-wrinkle effects were evaluated with two methods: (i) doctors' observation and photographs based on the guideline of the Japan Cosmetic Industry Association; and (ii) average roughness of skin surface (Ra value) using skin replica. This cosmetic showed marked and moderate improvement in 64% of the subjects with a significant difference as compared with the control site (P0.001). Wrinkle grades in the tested area significantly reduced more than pre-application (P0.001) and the control (P0.001). Reduction in Ra value on the tested area was more than pre-application (P0.01) and the control site (P0.05) with significant differences. Only one subject stopped the study with minimal irritation. These results indicated that the tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles in the eye areas.

Pigmented mammary Paget's disease is a rare variant of mammary Paget's disease. The clinical appearance mimics malignant melanoma. This paper describes a case of asymptomatic, slightly pigmented spots on the right mammary nipple. The pigmented nipple was histopathologically diagnosed as mammary Paget's disease with an underlying intraductal carcinoma. This case suggests the importance of conducting skin biopsies of developing pigmented spots on the nipples in elderly people.

Intense pulsed light (IPL) therapy improves various clinical symptoms of photoaging skin. In this study we have investigated clinical effects of a novel IPL, Lumenis One™ (LUMENIS, Tokyo) on facial pigmentary lesions in 18 Japanese female patients. Measurement was performed after 3–5 treatments. IPL showed marked and slight improvements in 28 and 39%, respectively. The data of melanin index demonstrated the improvement after IPL therapy. These results indicated that IPL therapy using Lumenis One may be useful to treat solar lentigines and ephelides on the face.

Recently, we reported an evaluation method with computer analysis of the video-captured digital image for whitening effects of cosmetics. In this study we have developed a new evaluation method of change of skin color using Robo Skin Analyzer that analyzes digital-camera-captured image. We have also investigated whitening effects of an intense pulsed light (IPL), NatuLight™ (LUMENIS, Tokyo), on skin color of the face in 27 Japanese female patients. Measurement was performed after three to five treatments. Whitening effects were evaluated in pigmentary and normal areas. IPL showed improvement in Value data (lightness) of the pigmentary and normal areas. In 16 (59%) of 27 patients IPL had whitening effects on the pigmentary lesions. In 18 (66%) of 27 patients IPL also demonstrated whitening effects on normal skin. Fourteen patients (52%) showed whitening effects both on pigmentary and normal areas. These results indicated that IPL therapy may have a whitening effect both on pigmentary and normal areas of the face. This novel method may be useful to evaluate the whitening effect of phototherapy and color change of cutaneous disorders.

Objective methods of measuring skin color are needed to evaluate pigmentary lesions quantitatively. We have developed a new method of measuring skin color using a plastic bar system called the Skin Tone Color Scale based on Munsell's color space system. We have also evaluated the effectiveness of various therapies using this measurement system. Our system was designed to measure skin color in normal skin, pigmentary lesions of solar lentigo, chloasma and ephelides, and postinflammatory pigmentation. Moreover, effectiveness of various therapies for these pigmentary lesions was evaluated. The evaluations made with this system were closely related to physician assessment. This method may be useful in measuring of skin color and evaluating the effectiveness of therapies for pigmentary diseases.

To investigate the distribution of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies among patients with autoimmune diseases, and to analyze the clinical features of patients with dermatomyositis (DM) with anti-ARS antibodies.Serum samples from 315 patients with autoimmune diseases or related disorders who had visited Kanazawa University Hospital or affiliated facilities were assessed for anti-ARS antibodies by immunoprecipitation. In particular, the association between anti-ARS antibodies and clinical features was investigated in detail in patients with DM.Anti-ARS antibody was positive in 16 (29%) of 55 patients with DM, 2 (22%) of 9 patients with polymyositis, and 7 (25%) of 28 patients with idiopathic pulmonary fibrosis. Although anti-ARS antibody was detected with high frequency (63%, 15/24) in DM patients with interstitital lung disease (ILD), the incidence of anti-ARS antibody was very low (3%, 1/31) in DM patients without ILD. Anti-ARS antibody-positive patients with DM had significantly higher incidences of ILD (94% vs 23%) and fever (64% vs 10%) than the antibody-negative patients. Some immunosuppressive agents, in addition to oral corticosteroids, were required more frequently in the antibody-positive patients with DM than the antibody-negative patients (88% vs 26%). Although 60% of DM patients with ILD simultaneously developed ILD and myositis, ILD preceded myositis in 33% of patients.Among patients with DM, anti-ARS antibodies are found in a subset with ILD. DM patients with anti-ARS antibodies appear to have a more persistent disease course that requires additional therapy compared to those without anti-ARS antibodies.

Skin fibrotic disorders such as systemic sclerosis (SSc) are characterized by an excessive production of extracellular matrix (ECM) and understood to develop under the influence of certain growth factors. Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-beta (TGF-beta). To better understand the mechanisms of persistent fibrosis seen in SSc, we previously established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, TGF-beta transiently induced subcutaneous fibrosis and serial injections of CTGF after TGF-beta caused persistent fibrosis. To further define the mechanisms of skin fibrosis induced by TGF-beta and CTGF in vivo, we investigated in this study, the effects of growth factors on the promoter activity of the proalpha2 (I) collagen (COL1A2) gene in skin fibrosis. For this purpose, we utilized transgenic reporter mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial beta-galactosidase gene. Serial injections of CTGF after TGF-beta resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-beta alone on day 8. We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-beta in comparison with the injection of TGF-beta alone. Furthermore, the serial injections recruited mast cells and macrophages. The number of mast cells reached a maximum on day 4 and remained relatively high up to day 8. In contrast to the kinetics of mast cells, the number of macrophages was increased on day 4 and continued to rise during the subsequent consecutive CTGF injections until day 8. These results suggested that CTGF maintains TGF-beta-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts. The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis.

The role of many growth factors and cytokines in the process of wound healing has been intensively investigated in recent two decades. Among them, transforming growth factor-βs (TGF-βs) are well known to have a potent stimulatory effect on collagen synthesis as shown in various in vivo experimental systems. In the present study, we examined the effects of various growth factors on the promoter activity of the proα2 (I) collagen gene (COL1A2) during the wound healing process. For this purpose, we utilized transgenic mice harboring the −17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase or a bacterial β-galactosidase gene. These mice exhibited normal phenotypic expression and the wound healing process was not impaired. Full thickness wounds were made by punch biopsy. We examined the effects of TGF-β1, -β2, -β3, basic fibroblast growth factor, platelet-derived growth factor, and connective tissue growth factor by applying them locally to the open wound every 2 days. Among the growth factors examined, all of the three isoforms of TGF-β exhibited a more potent stimulatory effect on COL1A2 promoter activity than did other factors. In addition, while TGF-β1 and -β2 significantly increased the number of fibroblasts which were positive for X-Gal staining, TGF-β3 treatment did not change the number of β-galactosidase expressing cells. Accumulation of collagen fibers was observed to the same extent in the mice treated with TGF-β1 and those with TGF-β3. These findings suggest that TGF-β1 and -β3 have similar but not identical regulatory mechanisms of COL1A2 expression, and that their pathophysiological roles in wound healing might be different from each other. J. Cell. Physiol. 190: 375–381, 2002. © 2002 Wiley-Liss, Inc.