biostudies-literatureWang ZNational Natural Science Foundation of Chinae04552https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499418biostudies-literatureUnknown12(37)Progressive cardiac fibrosis post myocardial infarction (MI) drives pathological remodeling and heart failure, yet the role of endoplasmic reticulum-selective autophagy (ER-phagy) in this process remains unclear. Autocrine Motility Factor Receptor (AMFR) is a recently identified ER-phagy regulator, whose function under myocardial pathology remains poorly understood. Here, it is found that FAM134B-mediated ER-phagy activity is elevated in fibrotic mouse heart tissues post-MI and in cardiac fibroblasts stimulated by TGF-β1. AMFR knockout in mice aggravated cardiac fibrosis post-MI and worsened cardiac function, with scRNA-seq analysis demonstrating that AMFR-null cardiac fibroblasts exhibit a myofibroblast phenotype. Simultaneously, AMFR overexpression in cardiac fibroblasts reduces the exprAdvanced science (Weinheim, Baden-Wurttemberg, Germany)ER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway.PMC1249941882271592Jin XLi TNiu KYang BChen YLin YWang XJin YWang ZLiu WfalseER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway.Progressive cardiac fibrosis post myocardial infarction (MI) drives pathological remodeling and heart failure, yet the role of endoplasmic reticulum-selective autophagy (ER-phagy) in this process remains unclear. Autocrine Motility Factor Receptor (AMFR) is a recently identified ER-phagy regulator, whose function under myocardial pathology remains poorly understood. Here, it is found that FAM134B-mediated ER-phagy activity is elevated in fibrotic mouse heart tissues post-MI and in cardiac fibroblasts stimulated by TGF-β1. AMFR knockout in mice aggravated cardiac fibrosis post-MI and worsened cardiac function, with scRNA-seq analysis demonstrating that AMFR-null cardiac fibroblasts exhibit a myofibroblast phenotype. Simultaneously, AMFR overexpression in cardiac fibroblasts reduces the expr2025-01-01T00:00:00Z2025 Oct2026-06-04T04:47:11.078Z2026-05-05T03:12:39.014ZS-EPMC124994184067387010.1002/advs.202504552