Sardella, C, Winkler, C, Quignodon, L, Hardman, J, Toffoli, B, Giordano Attianese, G M P, Hundt, J E, Michalik, L, Vinson, C R, Paus, R, Desvergne, B & Gilaardi, F 2018, ' DELAYED HAIR FOLLICLE MORPHOGENESIS AND HAIR FOLLICLE DYSTROPHY IN A LIPOATROPHY MOUSE MODEL OF Pparg TOTAL DELETION ', The Journal of Investigative Dermatology, vol. 138, no. 3 . https://doi.org/10.1016/j.jid.2017.09.024Test
PPARγ regulates multiple aspects of skin physiology, including sebocyte differentiation, keratinocyte proliferation, epithelial stem cell survival, adipocyte biology, and inflammatory skin responses. However, the effects of its global deletion, namely of nonredundant key functions of PPARγ signaling in mammalian skin, are yet unknown because of embryonic lethality. Here, we describe the skin and hair phenotype of a whole-body PPARγ-null mouse (PpargΔ/Δ), obtained by preserving PPARγ expression in the placenta. PpargΔ/Δ mice exhibited total lipoatrophy and complete absence of sebaceous glands. Right after birth, hair follicle (HF) morphogenesis was transiently delayed, along with reduced expression of HF differentiation markers and of transcriptional regulators necessary for HF development. Later, adult PpargΔ/Δ mice developed scarring alopecia and severe perifollicular inflammation. Skin analyses in other models of lipodystrophy, AZIPtg/+ and Adipoq-Cretg/+Ppargfl/fl mice, coupled with skin graft experiments, showed that the early defects observed in hair morphogenesis were caused by the absence of adipose tissue. In contrast, the late alteration of HF cycle and appearance of inflammation were observed only in PpargΔ/Δ mice and likely were due to the lack sebaceous glands. Our findings underscore the increasing appreciation for the importance of adipose tissue-mediated signals in HF development and function.
