{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE292nnn/GSE292393/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292393"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Fibrogenic macrophages drive cardiac fibrosis via MMP12-mediated tissue remodeling","description":"Fibrosis is a major contributor to mortality in various diseases, yet, it isunderlying mechanisms remain unclear. Here, we identified a mechanistic driver of fibrosis by investigating a fibrotic cardiac sarcoidosis mouse model. We demonstrate that mTORC1 induced a recently described fibrogenic macrophage population expressing Cd63, Spp1, Gpnmb, and Fabp5. sc-RNAseq analysis revealed a stepwise differentiation process of monocytes into fibrogenic macrophages via TGFβ signaling under mTORC1 control. Crucially, we uncovered matrix metalloproteinase 12 (MMP12) as the key effector that enables fibrogenic macrophages to mediate fibrosis. Pharmacologic inhibition of MMP12 diminished fibroblast activation, granulomatous inflammation, and resolved fibrotic lesions in the myocardium. Analysis of human cardiac sarcoidosis tissue and transcriptomics data from human liver and lung fibrotic diseases suggests MMP12-driven fibrotic remodeling by macrophages as conserved pathogenic mechanism. These findings provide a mechanistic basis for fibrogenic macrophage function and establish MMP12 as promising therapeutic target for fibrotic disease and cardiac sarcoidosis.","dates":{"publication":"2026/06/30"},"accession":"GSE292393","cross_references":{"GSM":["GSM8858309","GSM8858310","GSM8858303","GSM8858304","GSM8858302","GSM8858307","GSM8858308","GSM8858305","GSM8858306"],"GPL":["24247"],"GSE":["292393"],"taxon":["Mus musculus"]}}