Fig 1: Piezo1 activated epicardial-to-fibroblasts communication via Chemerin-Cmklr1 paracrine signaling.a UMAP projection of cardiac fibroblasts subclusters. b Proportional distribution of cardiac fibroblasts subclusters across experimental groups. c CellChat analysis reveals comparative signaling pathways between epicardial cells and fibroblasts, green denotes fibroblast-derived signaling pathways; blue indicates ECM signaling pathways involving epicardial cells; red represents epicardial-derived secretory signaling pathways; and black corresponds to epicardial-derived contact signaling pathways. d Network diagram of Chemerin signaling pathways among epicardial cell and fibroblast subclusters. e Wt1-Cre lineage mice were crossed with Rarres2fl/fl mice to generate epicardial-specific Rarres2 knockout (Rarres2CKO) mice. Echocardiography and sample collection were performed 5 weeks after sham operation or TAC. f Echocardiographic analysis of Rarres2fl/fl and Rarres2CKO mice 5 weeks after surgery, including measurements of left ventricular ejection fraction (LVEF), left ventricular internal diameter at systole (LVIDs), and left ventricular internal diameter at diastole (LVIDd) (n = 6 Rarres2fl/fl [Sham], 10 Rarres2CKO [Sham], 10 Rarres2fl/fl [TAC], 10 Rarres2CKO [TAC]). g Representative hematoxylin-eosin (HE)-stained longitudinal heart sections (n = 6 per group; scale bar = 2 mm). h Representative Masson’s trichrome-stained sections of LV tissues and quantitative analysis of fibrosis area in mice after surgery (n = 6 per group; scale bar = 50 μm). i Representative picrosirius red (PSR)-stained sections of LV tissues and quantitative analysis of fibrosis area in mice after sham operation or TAC (n = 6 per group; scale bar = 50 μm). j Western blot analysis and quantification of Fn1, Col1a1, and α-SMA protein levels in LV tissue homogenates from Rarres2fl/fl and Rarres2CKO mice 5 weeks after surgery (n = 4 per group). k Representative immunofluorescence staining images of Col1a1 (red), Cmklr1 (green), and α-SMA (purple) in LV tissues after sham operation or TAC (n = 4 per group; scale bar = 20 μm), along with the relative fluorescence intensity of Cmklr1. Panels i-viii display magnified representative views of each group (scale bar = 10 μm). Data are presented as mean ± standard deviation (Figures f, h, i, j, and k). For Figures f, h, i, j, and k, a two-way analysis of variance (ANOVA) followed by Tukey’s test was performed. A P-value < 0.05 was considered statistically significant.