Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion

Chiara Sardella, Carine Winkler, Laure Quignodon, Jonathan A. Hardman, Barbara Toffoli, Greta Maria Paola Giordano Attianese, Jennifer E. Hundt, Liliane Michalik, Charles R. Vinson, Ralf Paus, Béatrice Desvergne, Federica Gilardi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)500-510
Number of pages11
JournalJournal of Investigative Dermatology
Volume138
Issue number3
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

Hair Follicle
Morphogenesis
Peroxisome Proliferator-Activated Receptors
Skin
Sebaceous Glands
Hair
Adipose Tissue
Skin Physiological Phenomena
Inflammation
Lipodystrophy
Tissue
Differentiation Antigens
Alopecia
Keratinocytes
Adipocytes
Placenta
Physiology
Cicatrix
Stem cells
Cell Survival

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Sardella, C., Winkler, C., Quignodon, L., Hardman, J. A., Toffoli, B., Giordano Attianese, G. M. P., ... Gilardi, F. (2018). Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion. Journal of Investigative Dermatology, 138(3), 500-510. https://doi.org/10.1016/j.jid.2017.09.024

Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion. / Sardella, Chiara; Winkler, Carine; Quignodon, Laure; Hardman, Jonathan A.; Toffoli, Barbara; Giordano Attianese, Greta Maria Paola; Hundt, Jennifer E.; Michalik, Liliane; Vinson, Charles R.; Paus, Ralf; Desvergne, Béatrice; Gilardi, Federica.

In: Journal of Investigative Dermatology, Vol. 138, No. 3, 01.03.2018, p. 500-510.

Research output: Contribution to journalArticle

Sardella, C, Winkler, C, Quignodon, L, Hardman, JA, Toffoli, B, Giordano Attianese, GMP, Hundt, JE, Michalik, L, Vinson, CR, Paus, R, Desvergne, B & Gilardi, F 2018, 'Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion', Journal of Investigative Dermatology, vol. 138, no. 3, pp. 500-510. https://doi.org/10.1016/j.jid.2017.09.024
Sardella, Chiara ; Winkler, Carine ; Quignodon, Laure ; Hardman, Jonathan A. ; Toffoli, Barbara ; Giordano Attianese, Greta Maria Paola ; Hundt, Jennifer E. ; Michalik, Liliane ; Vinson, Charles R. ; Paus, Ralf ; Desvergne, Béatrice ; Gilardi, Federica. / Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 3. pp. 500-510.
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