Peroxisome Proliferator-Activated Receptor-γ Signalling Protects Hair Follicle Stem Cells from Chemotherapy-Induced Apoptosis and Epithelial-Mesenchymal Transition

January 2022 in “ British journal of dermatology/British journal of dermatology, Supplement ”

Ilaria Piccini, Lars Brunken, Jérémy Chéret, Sushmita Ghatak, Yuval Ramot, Majid Alam, Talveen S. Purba, Jonathan A. Hardman, Hanieh Erdmann, Francisco Jiménez, Ralf Paus, Marta Bertolini

peroxisome proliferator-activated receptor-γ PPAR-γ hair follicle stem cells chemotherapy-induced alopecia epithelial–mesenchymal transition 4-hydroperoxycyclophosphamide cyclophosphamide apoptosis DNA damage N-acetyl-GED-0507-34-Levo NAGED EMT 4-HC

TLDR Activating PPAR-γ signalling can protect hair follicle stem cells from damage caused by chemotherapy.

The study investigated the role of epithelial hair follicle stem cells (eHFSCs) in permanent chemotherapy-induced alopecia (pCIA) and tested a potential preventive treatment. Human scalp hair follicles (HFs) were exposed to 4-hydroperoxycyclophosphamide (4-HC), a metabolite of the chemotherapy drug cyclophosphamide, which induced apoptosis, DNA damage, and pathological epithelial-mesenchymal transition (EMT) in eHFSCs. Pretreatment with the PPAR-γ modulator N-acetyl-GED-0507-34-Levo (NAGED) protected against these effects, preserving the eHFSCs. The findings suggest that PPAR-γ signalling could be a novel intervention strategy to prevent pCIA by targeting apoptosis, DNA damage, and EMT in eHFSCs.

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