PPARγ Signaling Modulation Protects From Hair Follicle Bulge Stem Cell Damage and Cyclophosphamide-Induced Hair Follicle Cytotoxicity

September 2019 in “ The journal of investigative dermatology/Journal of investigative dermatology ”

Ilaria Piccini, Jérémy Chéret, Sushmita Ghatak, Majid Alam, Jonathan A. Hardman, Hanieh Erdmann, Francisco Javier Jiménez, Chris Ward, Ralf Paus, Marta Bertolini

PPARγ signaling hair follicle bulge stem cells cyclophosphamide chemotherapy-induced alopecia 4HC cytotoxicity apoptosis CK15+ bulge cells epithelial-mesenchymal transition NAC-GED-0507-Levo PPARγ modulator PPAR gamma signaling HFeSCs chemotherapy-induced hair loss NACGED

TLDR PPARγ signaling modulation can protect hair follicle stem cells from chemotherapy-induced damage.

The study investigated the protective effects of PPARγ signaling modulation on hair follicle bulge stem cells (HFeSCs) against cyclophosphamide-induced damage, which can lead to permanent chemotherapy-induced alopecia (pCIA). Ex vivo treatment with the cyclophosphamide metabolite 4HC caused hair follicle cytotoxicity, apoptosis of CK15+ bulge cells, and epithelial-mesenchymal transition (EMT). Pretreatment with NAC-GED-0507-Levo (NACGED), a PPARγ modulator, provided relative protection against 4HC-induced cytotoxicity and EMT. The findings suggested that pCIA irreversibility might result from apoptosis and EMT-mediated destruction of CK15+ bulge eSCs, and that PPARγ signaling modulation could be a potential strategy for managing permanent hair loss in chemotherapy-treated patients.

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