Hair Follicle Elongation Research Articles

Induction of hair growth in hair follicle cells and organ cultures upon treatment with 30 kHz frequency inaudible sound via cell proliferation and antiapoptotic effects.

Androgenic alopecia is a hair loss disease mediated by dihydrotestosterone (DHT) and is currently treated using minoxidil, finasteride, or low-level laser therapy. However, these treatments have side-effects, indicating the need for an alternative treatment. In the present study, it was demonstrated that inaudible sound at 30 kHz significantly induced proliferative and anti-apoptotic effects in human dermal papilla cells (hDPCs) and outer root sheath keratinocytes. Cell viability assay, ELISA, reverse transcription quantitative PCR and TUNEL assays were performed to evaluate the effect of inaudible sound. Inaudible sound was also demonstrated to significantly inhibit the hair loss signals induced by DHT treatment in hDPCs. Furthermore, inaudible sound significantly induced hair follicle (HF) elongation and hair matrix keratinocyte proliferation in human HF organ culture. Overall, the results suggested that inaudible sound may be effective in treating hair loss and could be used to develop a new hair loss treatment approach.

Feature-Based Molecular Networks Identification of Bioactive Metabolites from Three Plants of the Polynesian Cosmetopoeia Targeting the Dermal Papilla Cells of the Hair Cycle.

The term cosmetopoeia refers to the use of plants in folks’ cosmetics. The aerial parts of Bidens pilosa L., the leaves of Calophyllum inophyllum L. and the fruits of Fagraea berteroana A.Gray ex Benth are traditionally used in French Polynesia for hair and skin care. During the hair cycle, dermal papilla cells and their interaction with epithelial cells are essential to promote hair follicle elongation. The aim of our investigations was the identification of metabolites from these three plants and chemical families responsible for their hair growth activity. A bioactivity-based molecular network was produced by mapping the correlation between features obtained from LC-MS/MS data and dermal papilla cell proliferation, using the Pearson correlation coefficient. The analyses pointed out glycosylated flavonols and phenolic acids from B. pilosa and C. inophyllum, along with C-flavonoids, iridoids and secoiridoids from F. berteroana, as potential bioactive molecules involved in the proliferation of hair follicle dermal papilla cells. Our results highlight the metabolites of the plant species potentially involved in the induction of hair follicle growth and support the traditional uses of these plants in hair care.

Adiponectin negatively regulates pigmentation, Wnt/β-catenin and HGF/c-Met signalling within human scalp hair follicles ex vivo.

Adiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth.

Histopathological Differentiation of Antemortem and Postmortem Electrical Burn Mark Produced by Low Voltage.

The study was undertaken to differentiate antemortem electrical (AME) and postmortem electrical (PME) burn marks with the help of histopathology. The electrical burn mark was produced on 25 dead bodies. Alongside 25 cases of electrocution deaths were included for comparison. Slides were prepared and stained with hematoxylin-eosin stains. Intraepidermal and subepidermal separation; coagulative necrosis of the epidermis; nuclear elongation and hyperchromasia of epidermal cells; homogenization of the dermis; nuclear elongation and hyperchromasia of hair follicles, sweat glands, sebaceous glands, and blood vessel endothelium were studied for histopathological changes and graded. The findings of the study suggest that the histopathological changes in electrical burn marks are due to the physical effect of heat produced by the electric current. The classical histopathological features of electrical burn mark cannot differentiate between AME and PME burn marks. However, careful evaluation of grading of the dermal changes can be helpful in differentiating AME and PME burn marks. Highest grade of dermal thickness homogenization and highest grade of nuclear elongation of dermal appendages were significantly more in the antemortem electrical burn marks than PME burn marks.

Melatonin promotes Cashmere goat (Capra hircus) secondary hair follicle growth: a view from integrated analysis of long non-coding and coding RNAs

ABSTRACT The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an in vitro Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes.

The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick hair in Japanese men with androgenetic alopecia.

A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. This study focused on the ability of the peptide to promote human hair growth. 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. The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μm (P < 0.01), and 5.0 μm 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. 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.

Estrogen Leads to Reversible Hair Cycle Retardation through Inducing Premature Catagen and Maintaining Telogen

Estrogen dysregulation causes hair disorder. Clinical observations have demonstrated that estrogen raises the telogen/anagen ratio and inhibits hair shaft elongation of female scalp hair follicles. In spite of these clinical insights, the properties of estrogen on hair follicles are poorly dissected. In the present study, we show that estrogen induced apoptosis of precortex cells and caused premature catagen by up-regulation of TGF β2. Immediately after the premature catagen, the expression of anagen chalone BMP4 increased. The up-regulation of BMP4 may further function to prevent anagen transition and maintain telogen. Interestingly, the hair follicle stem cell niche was not destructed during these drastic structural changes caused by estrogen. Additionally, dermal papilla cells, the estrogen target cells in hair follicles, kept their signature gene expressions as well as their hair inductive potential after estrogen treatment. Retention of the characteristics of both hair follicle stem cells and dermal papilla cells determined the reversibility of the hair cycle suppression. These results indicated that estrogen causes reversible hair cycle retardation by inducing premature catagen and maintaining telogen.

The Hair Growth Effect of Polygoni mulitiflori Radix Water Extracts in C57BL/6 Mice

This study was carried out to investigate the effect of Polygoni mulitiflori Radix water extracts (PMWE) on hair growth and hair follicle development in C57BL/6 mice. Six weeks old female mice were divided into 4 groups including normal group (saline, N), vehicle control group (jojoba oil+100% ethanol+saline, VC), positive control group (3% minoxidil, PC), and experimental group (PMWE, E), and they were topically applied with an amount of 0.2 mL experimental compounds once a day, 6 days a week for 4 weeks. Hair regrowth was evaluated by the gross examination. Topical treatment of PMWE and 3% minoxidil to dorsal skin accelerated hair regrowth faster than N and VC groups. E and PC groups promoted development and elongation of hair follicles compared with N and VC groups. In week 4, absolute weight of heart and spleen were significantly heavy in PC group compared with N, VC and E groups. Relative weight of spleen was significantly heavy in PC group compared with N and VC groups. Relative weight of right kidney was significantly light in PC group compared with N, VC and E groups. Whereas absolute and relative weight of thymus were significantly light in E group compared with N group (p⁄0.05). In week 4, there was significantly high value of RBC count in PC group compared with N and VC groups, and significantly low value of platelet count in PC group compared with N group(p⁄0.05). These results indicate that PMEW effectively stimulated hair growth with development of hair follicle in an animal model and that it showed more safer than minoxidil.

Fluorine-Induced Apoptosis and Lipid Peroxidation in Human Hair Follicles In Vitro

Fluoride is an essential trace element for human body; however, exposure to high amounts of fluoride has been documented to be correlated with an increasing risk of hair loss. To date, little is known about the mechanism(s) of how fluoride affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little influence. Moreover, treatment with high levels of NaF resulted in a marked increase in terminal dUTP nick end labeling-positive cells in the outer layer of the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased oxidative stress manifested as higher malondialdehyde content. Additionally, the presence of selenium considerably antagonized the effects of middle NaF on hair follicles, with regard to either the suppression of hair growth or the induction of oxidative stress and apoptosis. In conclusion, exposure to high levels of fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro. The toxicity of fluoride can be reduced by selenium, at least partially via the suppression of intracellular oxidative stress.

Effect of Sodium Silicate on Hair Growth in C57BL/6 Mice

A promoting effect of Na₂SiO₃ on hair regrowth was investigated using an animal model of C57BL/6 mice. There were four experimental groups including distilled water (DW, a negative control), 5% minoxidil (MXD, a positive control), 50% Na₂SiO₃, and 100% Na₂SiO₃ solution. The animals were shaved with an electric clipper and then test solutions applied daily with a volume of 0.2 ㎖ per to the dorsal skin of mice for 3 weeks. Body weight and food and water consumption were measured weekly. Photographs of hair regrowth were taken at experimental day 0, 4, 7, 10, 14, 17, and 21. Activities of alkaline phosphatase and γ-glutamyl transpeptidase as well as expressions of growth factors were also determined in the dorsal skin of mice. The animal body weight were not significantly changed among the experimental groups. The MXD and Na₂SiO₃ accelerated hair regrowth compared with DW. The elongation of hair follicles were evidently observed in MXD and 50 or 100% Na₂SiO₃ groups. MXD significantly increased γ-glutamyl transpeptidase at day 14, compared with DW (P＜0.05). But the activities of alkaline phosphatase and γ-glutamyl transpeptidase were not significantly increased in Na₂SiO₃ groups, compared with DW. The expression of epidermal growth factor was significantly increased in MXD and Na₂SiO₃ groups, compared with DW (P＜0.05). The expression of vascular endothelial growth factor was not significantly changed by MXD or Na₂SiO₃ treatments. The expression of transforming growth factor (TGF)-β1 was clearly decreased in MXD and Na₂SiO₃ groups, compared with DW. These results indicate that Na₂SiO₃ may have a hair growth-promoting activity and it can be used for treatment of alopecia or boldness in humans.

A cell-based system for screening hair growth-promoting agents

Androgen-inducible transforming growth factor beta (TGF-beta1) derived from dermal papilla cells (DPCs) is a catagen inducer that mediates hair growth suppression in androgenetic alopecia (AGA). In this study, a cell-based assay system was developed to monitor TGF-beta1 promoter activity and then used to evaluate the effects of activated TGF-beta1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-beta1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-beta1 promoter activity was constructed. Treatment of HaCaT with dihydrotestosterone, which is known to be a primary factor of AGA, resulted in a concentration-dependent increase in TGF-beta1 promoter activity. However, treatment of HaCaT with the TGF-beta1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-beta1 expression. Subsequent use of this assay system to screen TGF-beta1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-beta1 expression. In addition, treatment with apigenin also significantly increased the proliferation of both SV40T-DPCs (human DPCs) and HaCaT cells. Furthermore, apigenin stimulated the elongation of hair follicles in a rat vibrissa hair follicle organ culture. Taken together, these findings suggest that apigenin, which is known to have antioxidant, anti-inflammatory, and anti-tumor properties, stimulates hair growth through downregulation of the TGF-beta1 gene. In addition, these results suggest that this assay system could be used to quantitatively measure TGF-beta1 promoter activity in HaCaT, thereby facilitating the screening of agents promoting hair growth.

Angiogenin is expressed in human dermal papilla cells and stimulates hair growth

The perifollicular vasculature undergoes hair-cycle dependent expansion and degeneration. Multiple soluble factors derived from dermal papilla cells (DPCs) may act on surrounding blood vessels to influence angiogenesis, growth and differentiation, and thereby regulate cyclic hair growth. The goal of this study was to examine the expression of angiogenin, a potent angiogenic factor, in human DPCs, and to determine its role in hair growth. Reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunofluorescence and ELISA analyzes were used to investigate the expression of angiogenin in human DPCs, while semi-quantitative RT-PCR was used to assess angiogenin mRNA expression in murine skin phased at different stages of the hair cycle. We detected angiogenin expression in DPCs, where it was found to be localized to the cytoplasm. Angiogenin mRNA was expressed in murine skin in a hair-cycle dependent manner, with maximum levels observed at the late anagen. Local injection of angiogenin promoted skin angiogenesis and induced anagen VI. In vitro studies showed that angiogenin significantly enhanced the elongation of hair follicles, and stimulated DPCs and ORS keratinocytes to proliferate. Taken together, these findings show that angiogenin is expressed in human DPCs, where it might contribute to hair growth directly, by stimulating DPCs and ORS keratinocytes to proliferate, or indirectly, by inducing local vascularization.

The effect of tripeptide-copper complex on human hair growth in vitro

The tripeptide-copper complex, described as a growth factor for various kinds of differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor, but decreased the secretion of transforming growth factor-beta1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts, which are important in the morphogenesis and growth of hair follicles. In the present study, the effects of L-alanyl-L-histidyl-L-lysine-Cu2+ (AHK-Cu) on human hair growth ex vivo and cultured dermal papilla cells were evaluated. AHK-Cu (10(-12) - 10(-9) M) stimulated the elongation of human hair follicles ex vivo and the proliferation of DPCs in vitro. Annexin V-fluorescein isothiocyanate/propidium iodide labeling and flow cytometric analysis showed that 10(-9) M AHK-Cu reduced the number of apoptotic DPCs, but this decrease was not statistically significant. The ratio of Bcl-2/Bax was elevated, and the levels of the cleaved forms of caspase-3 and PARP were reduced by treatment with 10(-9) M AHK-Cu. The present study proposed that AHK-Cu promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.

The water-soluble extract of Illicium anisatum stimulates mouse vibrissae follicles in organ culture.

It is well known that reduced blood flow in the scalp is a cause of alopecia. We have shown previously that the extract of Illicium anisatum increases subcutaneous blood flow in mice. In the present study, we used an organ culture system to examine whether this extract promoted hair follicle elongation. B6C3HF1 mouse vibrissae follicles were cultured in serum-free medium for 7 days at 31 degrees C. Follicles treated with water-soluble (WS) extracts of the leaves, fruits and roots of Illicium anisatum or shikimic acid grew significantly longer than controls. In contrast, ethyl acetate-soluble (AS) extracts and n-hexane-soluble (HS) extracts of the leaves, fruits and roots of the plant inhibited hair follicles and shaft growth. Fractionation of the WS fruit extract showed that the number 1 and number 2 fractions possessed hair follicle elongation activity. GC/MS analysis revealed that the number 1 fraction contained shikimic acid, and that the number 2 fraction was a mixture of many components including glycosides and polysaccharides. Reverse transcription-polymerase chain reaction analysis demonstrated that shikimic acid also induced mRNA expression of insulin-like growth factor-1, keratinocyte growth factor, and vascular endothelial growth factor in the hair follicles. These results suggest that the WS extract of Illicium anisatum promotes hair growth and may be a useful additive in hair growth products.

Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle

Background: Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle. Objective: To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth. Methods: We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture. Results: Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 μM and 351% at 1.0 μM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 μM and 257% at 1.0 μM of minoxidil. 1.0 μM of minoxidil increased Bcl-2 expression over 150%, while 1.0 μM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil. Conclusion: Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.

KF19418, a new compound for hair growth promotion in vitro and in vivo mouse models

KF19418, a newly synthesized compound, stimulated proliferation of cultured hair bulb cells from new born mice in concentration-dependent manner in the range under 10 μM. In the culture system of whole skin pieces from 4-week-old mice which we earlier established, KF19418 promoted hair follicle elongation as in the case of minoxidil. After topical application for 2 weeks of KF19418 or minoxidil to dorsal skin of hair-clipped mouse alopecia model, KF19418 at 1% suspension accelerated hair regrowth at a rate comparable to 1% minoxidil solution. Thus, it was shown that KF19418 directly stimulated hair follicle in vitro and had hair growth promoting activities in vivo.

Hepatocyte growth factor (HGF) activator expressed in hair follicles is involved in in vitro HGF-dependent hair follicle elongation

Hepatocyte growth factor (HGF), a paracrine factor secreted by follicular papilla cells, acts on neighboring follicular epithelial cells to promote follicular growth, while HGF activator is a serine proteinase, which converts inactive single-chain HGF to the active heterodimeric form. In this study, using 3′ rapid amplification of cDNA end/nested polymerase chain reaction (3′ RACE/nested PCR) and immunoblotting, we confirmed the expression of HGF activator in both cultured human follicular papilla cells and outer root sheath cells. HGF activator mRNA was expressed in all of the isolated 15 anagen hair follicles taken from the scalps of seven individuals. In an organ culture system, single-chain HGF stimulated hair follicle elongation, which was partially inhibited by aprotinin, a serine proteinase inhibitor ( P<0.01). These results suggest that single-chain HGF secreted from follicular papilla cells is converted to an active heterodimeric form by intrinsic HGF activator and that the resultant active form of HGF stimulates hair growth.

Distinct patterns of NCAM expression are associated with defined stages of murine hair follicle morphogenesis and regression.

Hair follicle development, growth (anagen), and regression (catagen) largely result from bidirectional epithelial-mesenchymal interactions whose molecular basis is still unclear. Because adhesion molecules are critically involved in pattern formation and because the fundamental importance of neural cell adhesion molecule (NCAM) for feather development has been demonstrated, we studied the protein expression patterns of NCAM during hair follicle development and regression in the C57BL/6 mouse model. During murine hair follicle development, NCAM immunoreactivity (IR) was first detected on epithelial hair placodes and later on selected keratinocytes in the distal outer root sheath. Mesenchymal NCAM immunoreactivity (IR) was noted on fibroblasts of the future dermal papilla (DP) and the perifollicular connective tissue sheath. Fetal hair follicle elongation coincided with strong, ubiquitous dermal NCAM IR, which remained strong until the follicles entered into their first neonatal catagen. At this time, the strong interfollicular dermal NCAM IR decreased substantially. During consecutive hair cycles, mesenchymal NCAM IR was seen exclusively on DP and perifollicular connective tissue sheath fibroblasts and on the trailing cells of regressing catagen hair follicles. These highly restricted and developmentally controlled expression patterns suggest an important role for NCAM in hair follicle topobiology during morphogenesis and cyclic remodeling of this miniorgan.

Hair follicle elongation in organ culture of skin from newborn and adult mice

By means of skin organ culture, some biological characteristics of hair follicle elongation were examined. When skin sections from 6-day-old C3H mice were cultured, spontaneous elongation of hair follicles was maintained. Without insulin, hair follicle elongation was poorly maintained irrespective of the presence of serum at 20%. Insulin could be replaced by IGF-I at 100 ng/ml. During in vitro elongation of hair follicles, bromodeoxyuridine was incorporated into germinal epithelial cells around dermal papillae. Skin sections from 4-week-old C3H mice did not show hair follicle elongation in complete medium. However, when 0.5 mM minoxidil was added to the medium, concentration dependent thickening and elongation of hair follicles was observed. In contrast, in vitro elongation of newborn pelage hair follicles was not enhanced by minoxidil. These results suggest that this system with the use of skin sections from 4-week-old C3H mice would be a potential in vitro model of human androgenic alopecia in which the anagen phase is suppressed but the suppression is partially released by minoxidil.

Hepatocyte growth factor/scatter factor expressed in follicular papilla cells stimulates human hair growth in vitro

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide which acts as mitogen, motogen, or morphogen. In this study, we examined the effect of HGF/SF on human hair growth using organ and cell culture systems. HGF/SF was found to stimulate hair length and DNA synthesis in hair follicles at increasing concentrations up to 10 ng/ml (P < 0.05 and P < 0.01, respectively). HGF/SF stimulated [3H]thymidine incorporation by hair bulb-derived keratinocytes with the strongest response at 30 ng/ml of HGF/SF (P < 0.05). Cultured follicular papilla cells secreted HGF/SF, measured by an enzyme-linked immunoassay, in response to interleukin 1-alpha (IL1-alpha, 10 ng/ml), tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml), or tetradecanoylphorbolacetate (100 nM) at levels ranging from 0.2 to 0.3 ng/mg protein/48 h. HGF/SF mRNA expressions, measured by the reverse transcription-polymerase chain reaction, were detected in follicular papilla cells, and were also stimulated by the three reagents. Transforming growth factor-beta (10 ng/ml) suppressed both protein and mRNA levels. These results suggest that hair follicle elongation induced by HGF/SF in organ culture occurs partly due to the mitogenic activity of HGF/SF expressed in follicular papilla cells on hair bulb-derived keratinocytes.