| First Author | Corano Scheri K | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 21 | PubMed ID | 36136606 |
| Mgi Jnum | J:334201 | Mgi Id | MGI:7387613 |
| Doi | 10.1172/jci.insight.160977 | Citation | Corano Scheri K, et al. (2022) SARA suppresses myofibroblast precursor transdifferentiation in fibrogenesis in a mouse model of scleroderma. JCI Insight 7(21) |
| abstractText | 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-beta+ 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-beta+ 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. |
