Sp1 mediates a therapeutic role of miR-7a/b in angiotensin II-induced cardiac fibrosis via mechanism involving the TGF-β and MAPKs pathways in cardiac fibroblasts

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Abstract

© 2015 Li et al. MicroRNA-7a/b (miR-7a/b) protects cardiac myocytes from apoptosis during ischemia/reperfusion injury; however, its role in angiotensin II (ANG II)-stimulated cardiac fibroblasts (CFs) remains unknown. Therefore, the present study investigated the anti-fibrotic mechanism of miR-7a/b in ANG II-treated CFs. ANG II stimulated the expression of specific protein 1 (Sp1) and collagen I in a dose- and time-dependent manner, and the overexpression of miR-7a/b significantly down-regulated the expression of Sp1 and collagen I stimulated by ANG II (100 nM) for 24 h. miR-7a/b overexpression effectively inhibited MMP-2 expression/activity and MMP-9 expression, as well as CF proliferation and migration. In addition, miR-7a/b also repressed the activation of TGF-β, ERK, JNK and p38 by ANG II. The inhibition of Sp1 binding activity by mithramycin prevented collagen I overproduction; however, miR-7a/b down-regulation reversed this effect. Further studies revealed that Sp1 also mediated miR-7a/b-regulated MMP expression and CF migration, as well as TGF-β and ERK activation. In conclusion, miR-7a/b has an anti-fibrotic role in ANG II-treated CFs that is mediated by Sp1 mechanism involving the TGF-β and MAPKs pathways.

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Li, R., Xiao, J., Qing, X., Xing, J., Xia, Y., Qi, J., … Ji, X. (2015). Sp1 mediates a therapeutic role of miR-7a/b in angiotensin II-induced cardiac fibrosis via mechanism involving the TGF-β and MAPKs pathways in cardiac fibroblasts. PLoS ONE, 10(4). https://doi.org/10.1371/journal.pone.0125513

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