Down-Regulation of Shh in the Hair Follicles of Mice During Chemotherapy-Induced Hair Loss Is Mediated by the JAK/STAT1 Signaling Pathway

November 2025 in “ FEBS Open Bio ”

Ruifang Fan, Jingling Huang, Xiang Lin, Tian Lan, Yuli Tang, Ling Sun, Guixuan Zhou

Sonic hedgehog Shh JAK/STAT1 signaling pathway chemotherapy-induced alopecia cyclophosphamide JAK inhibitors STAT1 hair follicles

TLDR JAK/STAT1 pathway causes hair loss during chemotherapy by reducing Shh in hair follicles.

This study investigates the mechanism behind chemotherapy-induced alopecia (CIA) by examining the role of the Sonic hedgehog (Shh) signaling pathway in Shh-GFP<sup>+/-</sup> mice. The researchers found that Shh-expressing cells in hair follicles significantly decreased after cyclophosphamide (CYP) treatment. Gene set enrichment analysis revealed upregulation of Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway-related genes. Chromatin immunoprecipitation assays showed increased binding of STAT1 to the Shh gene promoter during CIA. Treatment with JAK inhibitors rescued hair loss and increased Shh expression, highlighting the JAK/STAT1 pathway's role in regulating Shh during CIA. These findings offer new insights into the molecular mechanisms of CIA.

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