Matrix metalloproteinase 3 regulates angiotensin II‑induced myocardial fibrosis cell viability, migration and apoptosis.

Jin Shu, Yiwen Gu, Li Jin, Haiya Wang

Molecular medicine reports 2021 Feb

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Angiotensin II (AngII) is a central signaling molecule of the renin‑angiotensin system that serves a vital role in myocardial fibrosis (MF). The present study aimed to investigate the effects of matrix metalloproteinase (MMP)3 on MF progression. To induce cellular fibrosis, H9C2 rat myocardial cells were treated with AngII for 24 h. Subsequently, cells were treated with levocarnitine, or transfected with small interfering (si)RNA‑negative control or siRNA‑MMP3 (1/2/3). Cell viability, apoptosis and migration were assessed by performing Cell Counting Kit‑8, flow cytometry and Transwell assays, respectively. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting were performed to determine the expression levels of MF biomarkers, including disease‑, apoptosis‑ and oxidative stress‑related genes. Compared with the control group, AngII significantly inhibited H9C2 cell viability and migration, and significantly increased H9C2 cell apoptosis (P<0.05). However, compared with AngII‑treated H9C2 cells, MMP3 knockdown significantly inhibited fibrotic H9C2 cell viability and migration, but increased fibrotic H9C2 cell apoptosis (P<0.05). The RT‑qPCR results demonstrated that MMP3 knockdown significantly downregulated the expression levels of AXL receptor tyrosine kinase, AngII receptor type 1, α‑smooth muscle actin and Collagen I in AngII‑treated H9C2 cells (P<0.05). Moreover, compared with AngII‑treated cells, MMP3 knockdown significantly decreased Bcl‑2 expression levels , but significantly increased caspase‑3 and p53 expression levels in AngII‑treated cells (P<0.05). Additionally, compared with AngII‑treated cells, MMP3 knockdown significantly decreased MMP3, MMP9, STAT3, p22Phox and p47Phox expression levels in AngII‑treated cells (P<0.05). The present study indicated that MMP3 knockdown altered myocardial fibroblast cell viability, migration and apoptosis by regulating apoptosis‑ and oxidative stress‑related genes, thus delaying MF progression.

Citation

Jin Shu, Yiwen Gu, Li Jin, Haiya Wang. Matrix metalloproteinase 3 regulates angiotensin II‑induced myocardial fibrosis cell viability, migration and apoptosis. Molecular medicine reports. 2021 Feb;23(2)