{"doi":"10.1172/jci.insight.160977","title":"SARA suppresses myofibroblast precursor transdifferentiation in fibrogenesis in a mouse model of scleroderma","abstract":"We previously reported that Smad anchor for receptor activation (SARA) plays a critical role in maintaining epithelial cell phenotype. Here, we show that SARA suppressed myofibroblast precursor transdifferentiation in a mouse model of scleroderma. Mice overexpressing SARA specifically in PDGFR-β+ pericytes and pan-leukocytes (SARATg) developed significantly less skin fibrosis in response to bleomycin injection compared with wild-type littermates (SARAWT). Single-cell RNA-Seq analysis of skin PDGFR-β+ cells implicated pericyte subsets assuming myofibroblast characteristics under fibrotic stimuli, and SARA overexpression blocked the transition. In addition, a cluster that expresses molecules associated with Th2 cells and macrophage activation was enriched in SARAWT mice, but not in SARATg mice, after bleomycin treatment. Th2-specific Il-31 expression was increased in skin of the bleomycin-treated SARAWT mice and patients with scleroderma (or systemic sclerosis, SSc). Receptor-ligand analyses indicated that lymphocytes mediated pericyte transdifferentiation in SARAWT mice, while with SARA overexpression the myofibroblast activity of pericytes was suppressed. Together, these data suggest a potentially novel crosstalk between myofibroblast precursors and immune cells in the pathogenesis of SSc, in which SARA plays a critical role.","journal":"JCI Insight","year":2022,"id":275738,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945293,"name":"Xiaoyan Liang","orcid":"0009-0009-9873-4080","position":1,"is_corresponding":false},{"id":945294,"name":"Vidhi Dalal","orcid":"0000-0002-0656-9834","position":2,"is_corresponding":false},{"id":302546,"name":"I. Caroline Le Poole","orcid":"0000-0001-6853-4007","position":3,"is_corresponding":false},{"id":317086,"name":"John Varga","orcid":"0000-0001-8400-687X","position":4,"is_corresponding":false},{"id":917231,"name":"Tomoko Hayashida","orcid":"0000-0002-4160-7859","position":5,"is_corresponding":false},{"id":945292,"name":"Katia Corano Scheri","orcid":"0000-0002-2999-6556","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-19T00:28:21.971703Z","pmid":"36136606","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}