SARA suppresses myofibroblast precursor transdifferentiation in fibrogenesis in a mouse model of scleroderma

Katia Corano Scheri, Xiaoyan Liang, Vidhi Dalal, I. Caroline Le Poole, John Varga, Tomoko Hayashida*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere160977
JournalJCI Insight
Issue number21
StatePublished - Nov 8 2022

ASJC Scopus subject areas

  • Medicine(all)


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