Fig. 4

Fig. 4 Fibrotic roles of il11a in adult zebrafish hearts.

a Representative AFOG staining images of uninjured control and il11aOE hearts at 30 dpt (top), 3 mpt (middle), and 7 mpt (bottom). b Thickness of the collagen⁺ layer from Con and il11aOE at 3 and 7 mpt. Biological replicates = 8, 9, 9, and 8 for 3 mpt control, 3 mpt il11aOE, 7 mpt control, and 7 mpt il11aOE, respectively. c Differential expression of genes associated with regeneration (top), cardiac fibroblasts and pathological fibrosis (bottom) between 7 dpt and 7 mpt. Gene associated with fibrosis and fibroblasts are significantly upregulated in 7 mpt il11aOE hearts, compared to control, while those genes are not induced in 7 dpt il11aOE hearts. Expanded list of genes is in Supplementary Fig. 7a. d Representative cardiac section images of control and il11aOE hearts. Green and blue indicate Periostin (Postn)⁺ fibroblasts and DAPI, respectively. e Thickness of the Postn⁺ layer from Con and il11aOE at 10 and 30 dpt and 3 and 7 mpt. Biological replicates = 4 for all conditions, except 3 mpt control (n = 3). f Representative images of cardiac sections labeled with Postn (green) and tcf21:mCherry (red) at 30 dpt. Arrows indicate tcf21⁺ epicardial cells expressing Postn. g Colocalization assay of Postn⁺ cells with tcf21:mCherry⁺ layer. Biological replicates = 4 for control and il11aOE. h Representative cardiac section images stained with mCherry (red) and pERK (green) of 30 dpt Con and il11aOE hearts expressing tcf21:mCherry. i Quantification of pERK⁺ area in tcf21⁺ epicardium in the ventricles for Con and il11aOE. Biological replicates = 4 for control and il11aOE. j Dual roles of IL11 in the hearts. IL11 triggers cardiac regeneration programs, including CM proliferation and revascularization. Simultaneously, IL11 contributes to fibrosis by stimulating quiescent epicardial cells to generate epicardial progenitor cells (EPCs), which give rise to cardiac fibroblasts. Created in BioRender. Kang, J. (2024) BioRender.com/g25e465. Scale bars, 25 µm (top and middle) and 50 µm (bottom) in (a), 50 µm in (d), (f), and (h). Data are mean ± SEM in (b), (e), (g) and (i). p-values were determined by two-stage step-up multiple t-test in (b) and (e) and by unpaired two-tailed t-test in (g) and (i).