Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte‐mediated growth inhibition of anagen‐phase vibrissa hair

Abstract

tions in TEWL measurements of tape-stripped adult back skin (Fig. S3). ConclusionsIn summary, our results indicate that Calm4 is dispensable for epidermal barrier formation, skin homoeostasis, keratinocyte migration and wound healing. Calm4 À/À mice displayed no overt phenotypes and accordingly, their skin transcriptomes were very similar to wild-type controls. While we found no evidence of functional compensation by the highly homologous Calm5 or other Calmodulin isoforms, it is possible that other Ca 2+-binding proteins can functionally compensate for Calm4 in epidermal barrier formation and/or restoration, for example Calml3, which is highly expressed during the wound re-epithelialization stage in human skin (4). We also cannot rule out that Calm4 plays a nonredundant role in certain specialized responses to epidermal challenges that we did not address, for example pathogen exposure. However, the lack of an in vivo phenotype in mice genetically null for a small epidermal Ca 2+ -binding protein is not unique to Calm4. S100A9 À/À mice also appear grossly normal, even in several in vivo inflammatory assays, where S100A9 is normally expressed at high levels by both keratinocytes and skin-infiltrating leucocytes (9). Our findings therefore reinforce the notion that the establishment, maintenance and repair of the epidermal barrier are tightly regulated events involving a large and sometimes redundant assortment of signalling molecules. AcknowledgementsThe authors thank Dr. Gustavo Gutierrez-Cruz and Dr. Hong-Wei Sun for help with the RNAseq experiments, Kimberly Hilsen for assistance with mouse breeding and Dr. Mary Ann Stepp for input relating to the wound healing studies. This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (ZIA AR041124-15 to M.I. Morasso). Author contributionsJCL, AK and MIM designed the study; JCL and AK performed the research; JCL, AK, PB and MIM analyzed the data; JCL and MIM wrote the paper. Conflict of interestThe authors declare no conflict of interest. Supporting InformationAdditional supporting data may be found in the supplementary information of this article. Figure S1. Fig. 1g). Figure S2. Validation of RNAseq results by qPCR. Data is represented as the average of three biological replicates normalized to actin. Figure S3. Tape stripping of adult back skin leads to an increase in TEWL, but no significant differences between wild-type and Calm4 À/À . Appendix S1. Experimental design. 57Letter to the Editor result shows that leptin level is differentially expressed during hair cycle, the lowest in early anagen phase, upregulated in late anagen phase and the highest in the telogen phase. On the other hand, leptin receptor is detected in keratin 15-positive hair bulge epithelium of both anagen-and telogen-phase hair follicles of mice pelage and vibrissa hair, and hair from human scalp. Leptin contributes to adipocyte-mediated growth inhibition of anagenphase vibrissa hair as demonstrate...

The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration

“…Ablation of leptin signaling in db/db mice, mutant for leptin receptor, prominently delays anagen entry, while intradermal injection of leptin induces new anagen [30]. Moreover, at supra-physiological concentrations, leptin can inhibit anagen phase in vitro in cultured vibrissa follicles [31]. Future studies are needed to establish the contribution to hair cycle-modulating leptin from local paracrine sources (dermal WAT) vs. systemic sources that have no physical connection to hair follicles (visceral and deep subcutaneous WAT depots).…”

Hydrogel from Acellular Porcine Adipose Tissue Accelerates Wound Healing by Inducing Intradermal Adipocyte Regeneration

“…HAPA might activate the associated transcription factors by inducing adipocyte regeneration. Second, multiple cytokines secreted by newly formed adipocytes might contribute to appendage regeneration (Levin et al, 2011;Yang et al, 2015). Third, the adipogenic microenvironment might directly participate in skin appendage regeneration.…”

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia

“…revealed that leptin contributed to adipocyte‐mediated growth inhibition in the anagen phase. While that study was persuasive, the inhibitory effect was evaluated using a vibrissa culture system, and it is possible that the function of leptin in hair growth might differ between vibrissa and pelage hair . CLD typically shows a depressed lesion in the abdominal skin, whereas CLD of the scalp is characterized by reversible hair loss.…”