miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart

Figure 1

Fibrotic gene expression in fibroblasts after TGF-β stimulation. (a) Effects of EV-CPC^ISX-9 on fibrotic gene expression: role of miR-373. . (b) Transdifferentiation of lung fibroblasts and dermal fibroblasts into myofibroblasts by hypoxia for 72 h as detected by immunostaining for α-smooth actin (α-SMA): effects of EV-CPC^ISX-9 and miR-373 mimic pretreatment. . (c) Schematic representation of the luciferase reporter constructs. (d) Sequence alignment of miR-373 with the human wild-type (WT) ROCK-2 3-UTR and GDF-11 3-UTR and mutated reporters. The seed sequence (red) is highlighted. (e) Relative luciferase activity (relative, firefly luciferase activity/Renilla luciferase activity) of 293FT cells cotransfected with WT 3-UTR-ROCK-2 or GDF-11 and mutant 3-UTR-ROCK-2 or GDF-11 and miR-373 mimics vs. NC. , . UTR: untranslated region; miRNA: microRNA; NC: negative control; WT: wild type. (f) 72 h hypoxia increased GDF-11 and ROCK-2 mRNA expression in lung fibroblasts: effects of pretreatment with miR-373 mimic. . n = 6. (g) Pretreatment of fibroblasts during hypoxia with EV-CPC^ISX-9 significantly decreased the upregulation of GDF-11 and ROCK-2 similar to pretreatment with miR-373 mimic. . .

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