Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice

Kang, Byungjun; Shin, Sug Kyun; Kwack, Mi Hee; Shin, Hye‐Rim; Oh, Ji Won; Kim, Jin Oh; Moon, Chanil; Moon, Cheil; Kim, Jung Chul; Kim, Moon Kyu; Sung, Young Kwan

doi:10.1016/j.jdermsci.2010.04.015

Cited by 18 publications

(15 citation statements)

References 19 publications

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“…[Danilenko et al, 1996;Kang et al, 2010;Lefever et al, 2010]. For example, activin B, a homodimer subunit of activin, has been shown to stimulate the wound healing process [Wankell et al, 2001;Bamberger et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Activin B Promotes Initiation and Development of Hair Follicles in Mice

Jia

Zhang²,

Kong³

et al. 2013

Cells Tissues Organs

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Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated.In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice.

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Section: Discussionmentioning

confidence: 99%

Activin B Promotes Initiation and Development of Hair Follicles in Mice

Jia

Zhang²,

Kong³

et al. 2013

Cells Tissues Organs

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“…Amongst the group of receptors that are known to signal via the JAK-STAT5 pathway and have been implicated in the DP are erythropoietin receptor (EPOR) and prolactin receptor (PRLR). The DP has not only been shown to express EPOR, but there is evidence demonstrating that erythropoietin (EPO) promotes the induction of anagen from telogen, possibly by stimulating DP cells (Kang et al, 2010). These findings correspond with our data that suggests STAT5 activation is an anagen-inducing signal.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies exist that demonstrate EPOR presence within the DP and note STAT5 activation in DP cells in response to EPO (Kang et al, 2010;LeBaron et al, 2007). In vitro, EPO has been shown to promote hair shaft growth in cultured human hair follicles and in vivo experiments in mice have shown that EPO treatment in telogen skin induces anagen phase (Kang et al, 2010). In humans, recombinant EPO given for the treatment of chronic kidney failure was demonstrated to induce hypertrichosis in a modest proportion of patients (Kleiner et al, 1991;Tosi et al, 1994).…”

Section: Stat5 and The Dermal Papilla Control Of Hair Cyclingmentioning

confidence: 97%

“…Signalling pathways that have been implicated in the DP's control of anagen induction in adult hair cycling include those of EPOR, PDGFRα and FGF receptor (Kang et al, 2010;Kawano et al, 2005). Investigations into EPOR signalling specifically noted strong activation of STAT5 within the DP, and STAT5 is known to be implicated in PDGFRα and FGF receptor signal transduction (Kong et al, 2002;LeBaron et al, 2007;Piccaluga et al, 2014).…”

Section: Stat5amentioning

confidence: 99%

“…Investigations into EPOR signalling specifically noted strong activation of STAT5 within the DP, and STAT5 is known to be implicated in PDGFRα and FGF receptor signal transduction (Kong et al, 2002;LeBaron et al, 2007;Piccaluga et al, 2014). Activation of these receptors with their appropriate ligands has been shown to induce anagen in the adult mouse, and thus, these present as possible upstream signals that lead to activation of STAT5 in the DP (Kang et al, 2010;Kawano et al, 2005;Tomita et al, 2006). Therefore, deletion of STAT5 within the DP may be delaying anagen entry by inhibiting the aforementioned signalling pathways; however, this cannot be concluded in this study and requires further investigation.…”

Section: Stat5amentioning

confidence: 99%

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Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

Legrand¹

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The hair follicle is an important skin appendage that arises during development from complex reciprocal signalling between the epidermis and dermis. The multiple epidermal layers of the hair follicle are known to be under the control of the mesenchymal component, the dermal papilla (DP), which has been described as the key regulator of hair follicle induction and maintenance. The hair follicle has elicited interest as a model system for the investigation of tissue and organ regeneration due to its ability to regenerate completely throughout the life of a mammal. This characteristic is attributed to the reservoir of stem cells within the hair follicle, which is modulated by the DP.Although it is known that the DP is central to regulation of the hair follicle, mediators of its signalling are incompletely understood. Potential mediators of DP activity continue to emerge, two of which include the SoxF transcription factor, Sox18, and the transcription factor, STAT5. Sox18 has been implicated in hair type specification by the DP; however, its expression and function remains unclear. STAT5 has been shown in microarray analyses of the DP to be specifically expressed and upregulated, while studies involving STAT5 genetic knockouts display a hair phenotype. More recently, STAT5 has been implicated in autoimmune conditions affecting the hair follicle such as alopecia areata.To investigate further the role of STAT5 in the DP, I have hypothesised that STAT5 plays a key role in the DP's hair follicle inductive properties and regulation of cycling.STAT5 activation in the DP was characterised through immunofluorescence staining of mouse back skin at various stages of hair follicle development and cycling. Back skin was obtained from Topflash transgenic mice, a canonical Wnt reporter transgenic mouse driving luciferase expression, using β-catenin activity to monitor hair cycling via live bioluminescence imaging. While embryonic skin did not display any activation of STAT5, during postnatal hair follicle development (P0-P19), the majority of phospho-STAT5 positive DP were present within telogen phase, to a lesser extent within catagen and not at all during anagen. Adult skin showed phospho-STAT5 activation beginning in late catagen and persisting through to early anagen.Characterisation of SOCS2 by immunofluorescence, a downstream STAT5 transcriptional target, showed expression corresponding to the chronology of phospho-STAT5 activity.Hair regeneration assays were performed with DP cells using SKP culture with STAT5 activity modified through adenovirus constructs. SKPs derived from C57BL/6 neonates and STAT5 lox/lox neonates were transduced with STAT5A/B constitutively-active and crerecombinase constructs, respectively. These transduced SKPs were then used in patch assay experiments and DP formation was quantified using a green fluorescent protein ii (GFP) reporter. SKPs transduced with constitutively-active STAT5 were significantly better at forming hair follicle DP than control SKPs transduced with GFP alone. SKPs with...

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