Homocysteine Exacerbates Pulmonary Fibrosis via Orchestrating Syntaxin 17 Homocysteinylation of Alveolar Type II Cells.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease, marked by progressive extracellular matrix deposition, for which there are no effective treatments to halt disease progression. Although hyperhomocysteinemia is implicated in multiple pathological processes, its role in IPF remains largely unexplored. Through multiomics profiling of IPF patients, significantly elevated homocysteine (Hcy) concentrations in plasma and bronchoalveolar lavage fluid are identified compared to healthy controls. Single-cell RNA sequencing and spatial transcriptomics reveal alveolar type 2 epithelial cells as the primary site of Hcy metabolism, with downregulation of Hcy-catabolizing enzyme methionine synthase reductase (MTRR) during fibrotic progression. Genetic perturbation studies in mur

SUBMITTER: Huang J 

PROVIDER: S-EPMC12697838 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature