Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding

Kwon, Oh Sang; Zhang, Zhikun; Spata, Michelle; Plikus, Maksim V.; Holler, Phillip D.; Ito, Mayumi; Yang, Zeyong; Treffeisen, Elsa; Kim, Chang Deok; Nace, Arben; Zhang, Xiaohong; Baratono, Sheena; Wang, Fen; Ornitz, David M.; Millar, Sarah E.; Cotsarelis, George

doi:10.1038/nm.3181

Cited by 282 publications

(319 citation statements)

References 36 publications

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“…A more recent study from Gay et al (2013) showed the role of FGF9 secretion from gd-T Figure 2. Schematic illustration of molecular mechanisms during hair follicle morphogenesis (top) and neogenesis (bottom).…”

Section: Regeneration Of Skin Appendages-hair Follicle Neogenesismentioning

confidence: 99%

Wound Healing and Skin Regeneration

Takeo

Lee

Ito

2015

Cold Spring Harbor Perspectives in Medicine

494

319

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The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages to wound healing and, conversely, skin appendage regeneration following injuries.

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Section: Regeneration Of Skin Appendages-hair Follicle Neogenesismentioning

confidence: 99%

Wound Healing and Skin Regeneration

Takeo

Lee

Ito

2015

Cold Spring Harbor Perspectives in Medicine

494

319

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“…in the dermal fibroblasts during cutaneous wound healing. Although there are slight variations of activity levels with the wounds in other references (Gay et al, 2013;Whyte et al, 2013), these results are still correlated. Endothelin-1, a target of Wnt/-catenin pathway, was also specifically increased in the fibroblasts of CXXC5 / mouse wounds.…”

Section: Co-treatment With Ptd-dbm and Vpa Accelerates Cutaneous Wounmentioning

confidence: 71%

The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

Lee¹,

Kim²,

Kim³

et al. 2015

J Cell Biol

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Wnt/-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of -catenin, -smooth muscle actin (-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5 / mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)-Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated -catenin and collagen production in vitro. Cotreatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3 (GSK3) inhibitor which activates the Wnt/-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing.

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“…From having assumed that hair follicles are only created during embryogenesis, there is some evidence that new hair follicles can be created during wound healing Gay et al, 2013), giving hope to many researchers that one might eventually nd a cure for baldness.…”

Section: Hair Folliclesmentioning

confidence: 99%

“…. Cotsarelis, G. (2013 Physiol, 211(2), 353-363 Hennings, H., Holbrook, K., Steinert, P. and Yuspa, S. (1980). Growth and differentiation of mouse epidermal cells in culture: effects of extracellular calcium.…”

mentioning

confidence: 99%

Fibroblast Differentiation and Models of Human Skin

Rakar¹

2016

Linköping University Medical Dissertations

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Denna bok avhandlar en riktning av biomedicinsk forskning som i det långa loppet sy ar till att nå bättre och banbrytande sätt att läka våra kroppar. Forskningen vilar på en tredelad grund -viktiga kunskaper som leder mot en generell förståelse för hur celler blir till vävnader, hur vävnad-er och organ kan manipuleras på ett kliniskt användbart sätt, och till sist hur denna kunskap kan appliceras på människans hudorgan.Den första delen handlar om cellers identitet, och den stora potentialen som våra egna stamceller har för framtidens läkekonst. Genom att förstå hur celler egentligen fungerar på arvsmassenivå kan vi utöka arsenalen av verktyg vi har för att få celler att bete sig på de sätt som behövs för att skapa nya organ. Vi har jobbat med att karakterisera och manipulera broblaster, en av de vanligaste celltyperna i människokroppen, och bland annat tagit fram olika typer av fettceller.Den andra delen handlar om hur man använder celler, biokemiska faktorer och biokompatibla material för att konstruera vävnader och organ. Innan forskningen når klinisk användbarhet har vi möjlighet att bygga begränsade modellsystem för att studera människans biologi. Cellsystem på labbet är mycket viktiga verktyg för att föra forskningen på vävnadsbyg-gande framåt.Den tredje delen behandlar hudforskning speci kt, och här samlas kunskaper från tidigare delarna som är relevanta för mänsklig hud. Här beskrivs användningen av två olika hudmodeller för att undersöka proceser viktiga vid sårläkning. Vidare beskrivs planerna kring ett större påbörjat projekt som sy ar till att använda alla tidigare lärdomar och tekniker för att åstadkomma en ny terapi för sårläkning.Abstract is thesis combines three publications and one manuscript, covering two principal topics: functional di erentiation of human broblasts and, laboratory models of human skin. e two topics favourably unite in the realm of tissue engineering. is thesis is therefore split into three main parts: 1. a discussion of phenotypic plasticity as it pertains to broblasts and the stem cell continuum; 2. a short review of engineered tissue, with particular focus on soluble factors and materials; and, 3. a motivated review of the biology, diversity and culture of skin, including skin construction. e intended goal of our research endeavor was to achieve the formulation of a bioactive therapy for skin regeneration. e main hypothesis was that broblast-to-keratinocyte di erentiation would facilitate wound healing, and that the protocol for such a method could be adapted to clinical translation. e foundation for the hypothesis lay in the di erentiation capabilities of primary dermal broblasts (Paper I). However, the goal has not yet been achieved. Instead, intermediate work on the construction of skin for the purpose of creating a model test-bed has resulted in two other publications. e use of excised human skin, a formidable reference sample for tissue engineered skin, has been used to investigate a gelatin-based material in re-epithelialization (Paper II). A rst attempt at standardizi...

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Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding

Cited by 282 publications

References 36 publications

Wound Healing and Skin Regeneration

Wound Healing and Skin Regeneration

The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

Fibroblast Differentiation and Models of Human Skin

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