Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

Kwack, Mi Hee; Ahn, Ji Sup; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

doi:10.1038/jid.2011.274

Cited by 129 publications

(98 citation statements)

References 30 publications

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“…Cells were washed with phosphate-buffered saline and counterstained with hematoxylin for 10 minutes. HF specimens were immunostained as described before (Kwack et al, 2012) with isotype-matched normal rabbit IgG (R&D Systems) and Sox9 antibody as a negative control and a positive control, respectively.…”

Section: Immunostaining Of Sox9mentioning

confidence: 99%

Dickkopf 1 Promotes Regression of Hair Follicles

Kwack

Kim

et al. 2012

Journal of Investigative Dermatology

118

115

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Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of b-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagento-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.

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Section: Immunostaining Of Sox9mentioning

confidence: 99%

Dickkopf 1 Promotes Regression of Hair Follicles

Kwack

Kim

et al. 2012

Journal of Investigative Dermatology

118

115

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“…It was shown that DHT induces IL6 expression in the balding DP of human cells compared with nonbalding DP cells. This results in anagen-to-catagen transition in hair follicle and hair growth arrest [51]. Direction of the IL6 expression change by androgens is cell-specific.…”

Section: Dermal Papilla-specific Signaling Pathwaysmentioning

confidence: 99%

“…SPP1 (osteopontin) is expressed only during catagen but not in anagen or telogen in cultured rat vibrissae dermal papilla cells [115]. IL6 (interleukin 6) gene is a thoughtful candidate for DHT inducible catagen phase and regression of human hair shafts [51]. BMP2 is also a direct target of MIR106A [116].…”

Section: Hair and Scalp Disorders 154mentioning

confidence: 99%

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Nesterova¹,

Yuryev²

2017

Hair and Scalp Disorders

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Signaling pathways that control coordination of hair follicle cells genetic program are the convenient model for explaining the hierarchy of intercellular interactions governing cyclic growth of hair. This chapter describes models of molecular signaling pathways specific to dermal papilla cells from balding human scalp in hair follicle cycle. These models include already published data, as well as information inferred from pathway analysis of microarray data and protein-protein interaction database. Interplay of androgenic-alopecia-related signaling pathways FGF, TGFB, BMP, and WNT, as well as cyclin-dependent kinases signaling, is shown.

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“…method of paracrine signalling, it was shown that IL-6 acted on hair follicle keratinocytes to inhibit matrix cell proliferation and growth of the hair shaft, and consequently induced catagen (Kwack et al, 2012a). IL-6 has been previously demonstrated in vitro to mediate its effects via STAT5A in the JAK-STAT pathway, again implicating STAT5 in a further hair follicle signalling pathway in keratinocytes (Fujitani et al, 1997).…”

Section: Implications Of Stat5-mediated Signalling In the Hair Folliclementioning

confidence: 99%

“…STAT5 has appeared as part of signalling mechanisms within several investigations related to hair follicle cycling and as unpredicted side effects of other investigations; however, these investigations have not defined whether STAT5 could play an important role in the DP and the mesenchymal-epidermal interactions in these cells (Craven et al, 2006;Kwack et al, 2012a;Udy et al, 1997). Nevertheless, STAT5 appears at appreciable levels in microarray analyses in various investigations, and genetic knockout studies of STAT5 have shown to elicit a hair phenotype although its specific role in the DP compared to other skin components is unclear (Biernaskie et al, 2009;Driskell et al, 2009;Rendl et al, 2005;Udy et al, 1997).…”

Section: Summary and Significancementioning

confidence: 99%

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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Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

Cited by 129 publications

References 30 publications

Dickkopf 1 Promotes Regression of Hair Follicles

Dickkopf 1 Promotes Regression of Hair Follicles

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

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