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Hair follicle regeneration involves epithelial–mesenchymal interactions (EMIs) of follicular epithelial and dermal papilla (DP) cells. Co-grafting of those cellular components from mice allows complete hair reconstitution. However, regeneration of human hair in a similar manner has not been reported. Here, we investigated the possibility of cell-based hair generation from human cells. We found that DP-enriched cells (DPE) are more critical than epidermal cells in murine hair reconstitution on a cell number basis, and that murine DPE are also competent for hair regeneration with rat epidermal cells. Co-grafting of human keratinocytes derived from neonatal foreskins with murine DPE produced hair follicle-like structures consisting of multiple epidermal cell layers with a well-keratinized innermost region. Those structures expressed hair follicle-specific markers including hair keratin, and markers expressed during developmental stages. However, the lack of regular hair structures indicates abnormal folliculogenesis. Similar hair follicle-like structures were also generated with cultured human keratinocytes after the first passage, or with keratinocytes derived from adult foreskins, demonstrating that epidermal cells even at a mature stage can differentiate in response to inductive signals from DP cells. This study emphasizes the importance of EMI in follicular generation and the differentiation potential of epidermal keratinocytes.Journal of Investigative Dermatology (2007) 127, 2106–2115; doi:10.1038/sj.jid.5700823; published online 12 April 2007 [ABSTRACT FROM AUTHOR]

It has been previously reported that an adenosine receptor-mediated signal-transduction pathway in the dermal papilla cells (DPCs) of hair contributes to minoxidil-induced hair growth. In this study, we investigated this hypothesis further and have elucidated some underlying mechanisms. We performed DNA microarray analyses of DPCs and found that adenosine stimulation increases fibroblast growth factor-7 (FGF-7) gene expression levels by greater than 2-fold. Elevations of the extracellular FGF-7 protein levels were also observed. These upregulations of FGF-7 both at mRNA and protein levels were inhibited by A2b adenosine receptor-specific antagonist, alloxazine, but not by antagonists for other subtypes. In addition, the intracellular cAMP levels were raised by adenosine in a dose-dependent manner. Moreover, an increase of intracellular cAMP augmented the FGF-7 upregulation. Taken together, these results show that adenosine treatment of DPCs upregulates FGF-7 expression via the A2b adenosine receptor and that cAMP acts as one of the second messengers in this pathway. Furthermore, treatment with FGF-7 at concentrations of 10 ng/ml or greater significantly stimulated hair fiber elongation in human scalp hair follicle organ cultures. These data imply that adenosine might stimulate hair growth through FGF-7 upregulation in DPCs.Journal of Investigative Dermatology (2007) 127, 1318–1325. doi:10.1038/sj.jid.5700728; published online 15 February 2007 [ABSTRACT FROM AUTHOR]

Deals with a study which demonstrated that a short fragment of the human versican promoter is sufficient to activate lacZ reporter gene expression in the dermal papilla of postnatal transgenic mice. Coincidence of transgenic versican expression with endogenous messenger RNA expression; How versican promoter drives condensed mesenchyme-specific expression in embryonic transgenic skin; Loss of versican expression with cell passage.

A correction to the article "Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells," is presented.

Background A penta-peptide, Gly-Pro-Ile-Gly-Ser ( GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. Aim of this study This study focused on the ability of the peptide to promote human hair growth. Methods We used a human hair keratinocyte proliferation assay and organ cultures of human hair follicle as in vitro systems. The lotions with and without the penta-peptide were administered to 22 Japanese men with androgenetic alopecia (AGA) for 4 months in a double-blind and randomized clinical study. Results The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μ m ( P < 0.01), and 5.0 μ m of this peptide had a marked effect on hair shaft elongation in the organ culture ( P < 0.05). The change in the proportion of thick hair (≥60 μm) compared to baseline in patients that received the peptide was significantly higher than in the placebo ( P = 0.006). The change in the proportion of vellus hair (<40 μm) was also significantly lower in the peptide group than in the placebo ( P = 0.029). The penta-peptide also significantly improved the appearance of baldness ( P = 0.020) when blinded reviewers graded photographs of the participants according to a standardized baldness scale. No adverse dermatological effects due to treatment were noted during this clinical study. Conclusions This penta-peptide promotes proliferation of human hair keratinocytes and hair shaft elongation of human hair follicles, in vitro. This peptide increases thick hair ratio in vivo, and this compound is useful for the improvement of AGA. [ABSTRACT FROM AUTHOR]

Woolly hair (WH) is an abnormal variant of tightly curled hair, which is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal-dominant WH (ADWH) or autosomal-recessive WH (ARWH) inheritance patterns. ARWH has recently been shown to be caused by mutations in either the lysophosphatidic acid receptor 6 (LPAR6) or lipase H (LIPH) gene. More recently, a mutation in the keratin K74 (KRT74) gene has been reported to underlie ADWH. Importantly, all of these genes are abundantly expressed in the inner root sheath (IRS) of human hair follicles. Besides these findings, the molecular mechanisms underlying hereditary WH have not been fully disclosed. In this study, we identified a Japanese family with ADWH and associated hypotrichosis. After exclusion of known causative genes, we discovered the heterozygous mutation c.422T>G (p.Phe141Cys) within the helix initiation motif of the IRS-specific keratin K71 (KRT71) gene in affected family members. We demonstrated that the mutant K71 protein led to disruption of keratin intermediate filament formation in cultured cells. To our knowledge, it is previously unreported that the KRT71 mutation is associated with a hereditary hair disorder in humans. Our findings further underscore the crucial role of the IRS-specific keratins in hair follicle development and hair growth in humans. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) on keratinocytes are important cell surface receptors involved in the innate and acquired immune response to invading microorganisms. In acne vulgaris, TLR2 activation by Propionibacterium acnes (P. acnes) may induce skin inflammation via induction of various proinflammatory molecules that stimulate the invasion of inflammatory cells. Although corticosteroids themselves exert immunosuppressive or anti-inflammatory effects, it is well known clinically that systemic or topical glucocorticoid treatment provokes an acneiform reaction. Nevertheless, the effect of steroids on TLR2 expression in human keratinocytes remains unknown. Here, we found that the addition of glucocorticoids, such as dexamethasone and cortisol, to cultured human keratinocytes increased their TLR2 gene expression. Moreover, these glucocorticoids markedly enhanced TLR2 gene expression, which was further stimulated by P. acnes, tumor necrosis factor-α, and IL-1α. Gene expression of mitogen-activated protein kinase (MAPK) phosphatase-1 was also increased by the addition of dexamethasone. By using several inhibitors and activators, we found that TLR2 gene induction by glucocorticoids was mediated by the suppression of p38 MAPK activity following induction of MAPK phosphatase-1. These findings strongly suggest that steroid-induced TLR2 together with P. acnes existing as normal resident flora plays an important role in the exacerbation of acne vulgaris as well as in possible induction of corticosteroid-induced acne or in that of rosacea-like dermatitis.Journal of Investigative Dermatology (2009) 129, 375–382; doi:10.1038/jid.2008.237; published online 14 August 2008 [ABSTRACT FROM AUTHOR]