Dickkopf 1 Promotes Regression of Hair Follicles

Kwack, Mi Hee; Kim, Moon K.; Kim, Jung C.; Sung, Young Kwan

doi:10.1038/jid.2012.24

Cited by 118 publications

(125 citation statements)

References 32 publications

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“…In nonbald "normal" DP cell samples, we found that WNT signaling was lowered but still activated in bald DP samples. DKK1 was suggested as one of the key player of triggering catagen in AGA [45]. We could not detect significant DE of DKK1 in dataset 1.…”

Section: Cross-talk Between Pathways Affected In Aga Dp Cellsmentioning

confidence: 41%

“…In human bulge cells, increased expression of the WNT inhibitors WIF1 and DKK3 was also shown [60]. In patients with AGA, dermal papilla cells were shown to produce excessive amounts of factors inhibiting WNT signaling (for instance, DKK1) [45].…”

Section: Bulge Stem Cells Renewal Pathwaymentioning

confidence: 99%

“…Human DP cells from AGA express dihydrotestosterone-driven TGFB1, DKK1, and IL6 proteins. TGFB1, DKK1, and IL6 were able to promote apoptosis in outer root sheath keratinocytes derived from dermal papilla cells, which results in hair growth arrest [44][45][46].…”

Section: Dermal Papilla-specific Signaling Pathwaysmentioning

confidence: 99%

“…DKK1 acts as inhibitor of canonical WNT/CTNNB1 signaling and hair follicle growth in mice [49]. In mice, in cells of outer root sheath layer of hair follicle, recombinant human DKK1 as inhibitor of WNT induced the pro-apoptotic protein BAX, resulting in apoptosis [45].…”

Section: Dermal Papilla-specific Signaling Pathwaysmentioning

confidence: 99%

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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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Section: Cross-talk Between Pathways Affected In Aga Dp Cellsmentioning

confidence: 41%

Section: Bulge Stem Cells Renewal Pathwaymentioning

confidence: 99%

Section: Dermal Papilla-specific Signaling Pathwaysmentioning

confidence: 99%

Section: Dermal Papilla-specific Signaling Pathwaysmentioning

confidence: 99%

See 2 more Smart Citations

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Nesterova¹,

Yuryev²

2017

Hair and Scalp Disorders

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“…Recently, it has been suggested that Dkk1 expression in keratinocytes is involved in the hair follicle transition from anagen to catagen. Injection of recombinant human Dkk1 in mouse skin was found to induce catagen in hair follicle keratinocytes, by blocking Wnt signalling and upregulating expression of Bcl-2-associated X protein (Bax), a promoter of apoptosis, resulting in apoptosis of ORS keratinocytes (Kwack et al, 2012b).…”

Section: Hair Follicle Maintenance and Cyclingmentioning

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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Partial Proteasome Inhibitors Induce Hair Follicle Growth by Stabilizing β-Catenin

et al. 2014

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The activation of tissue stem cells from their quiescent state represents the initial step in the complex process of organ regeneration and tissue repair. While the identity and location of tissue stem cells are becoming known, how key regulators control the balance of activation and quiescence remains mysterious. The vertebrate hair is an ideal model system where hair cycling between growth and resting phases is precisely regulated by morphogen signaling pathways, but how these events are coordinated to promote orderly signaling in a spatial and temporal manner remains unclear. Here, we show that hair cycle timing depends on regulated stability of signaling substrates by the ubiquitin-proteasome system. Topical application of partial proteasomal inhibitors (PaPIs) inhibits epidermal and dermal proteasome activity throughout the hair cycle. PaPIs prevent the destruction of the key anagen signal β-catenin, resulting in more rapid hair growth and dramati cally shortened telogen. We show that PaPIs induce excess β-catenin, act similarly to the GSK3β antagonist LiCl, and antagonize Dickopf-related protein-mediated inhibition of anagen. PaPIs thus represent a novel class of hair growth agents that act through transiently modifying the balance of stem cell activation and quiescence pathways.

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Dickkopf 1 Promotes Regression of Hair Follicles

Cited by 118 publications

References 32 publications

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

Partial Proteasome Inhibitors Induce Hair Follicle Growth by Stabilizing β-Catenin

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