Cathepsin K Aggravates Pulmonary Fibrosis Through Promoting Fibroblast Glutamine Metabolism and Collagen Synthesis.

ABSTRACT: Fibroblast collagen synthesis is a hallmark of the pathogenesis and progression of pulmonary fibrosis (PF). However, the factors that trigger the abnormal activation of fibroblasts in PF are still not well understood. Using proteomics and single-cell sequencing dataset screening, extra accumulation of Cathepsin K (CTSK) is detected in the periphery as well as in fibroblasts in the lungs of PF mouse models. Addition of recombinant CTSK (rCTSK) aggravates collagen accumulation and PF progression in bleomycin-induced PF mice. Mechanically, CTSK underwent endocytosis through interaction with sorting nexin 9 (SNX9), which is engaged in TGF-β1 induced SMAD3 activation for downstream glutaminase 1 (GLS1) upregulation and glutamine enrichment. In turn, extra glutamine increases collagen synthesis

SUBMITTER: Chen M 

PROVIDER: S-EPMC12442634 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature