Key result
MMP3 knockdown significantly inhibited Angiotensin II-induced myocardial fibroblast cell viability and migration, and promoted apoptosis, delaying myocardial fibrosis progression.
Why the study?
Angiotensin II plays a vital role in myocardial fibrosis, but the effects of MMP3 on myocardial fibrosis progression required investigation.
Does MMP3 knockdown reduce AngII-induced myocardial fibrosis progression in H9C2 rat myocardial cells?
Does MMP3 knockdown reduce AngII-induced myocardial fibrosis progression in H9C2 rat myocardial cells?
p-value: p=<0.05
MMP3 knockdown attenuates AngII-induced myocardial fibrosis in vitro by regulating apoptosis and oxidative stress-related genes, suggesting MMP3 as a potential therapeutic target for heart failure.
MMP3 merits preclinical validation as antifibrotic target; leaves open translation from cell models to clinical fibrosis.
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.
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Jin et al. (2020) studied Myocardial fibrosis. MMP3 knockdown (siRNA-MMP3) vs. AngII-treated cells (siRNA-NC) was evaluated on Cell viability, apoptosis, and migration (p=<0.05). MMP3 knockdown significantly inhibited Angiotensin II-induced myocardial fibroblast cell viability and migration, and promoted apoptosis, delaying myocardial fibrosis progression.
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