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Published on: June 15, 2018
miR-135a Mediates Mitochondrial Oxidative Respiratory Function through SIRT1 to Regulate Atrial Fibrosis
Tianhang Ding1, Liyan Zeng1, Ying Xia1
1Department of Cardiovascular Medicine, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
Introduction:
This study aimed to explore the function of miR-135a in the progress of atrial fibrosis and the mechanism of miR-135a/SIRT1 (sirtuin 1) in human cardiac fibroblasts and mouse cardiac fibroblasts (MCFs) mediating the regulation of atrial fibrosis by mitochondrial oxidative respiration function.
Methods:
Using Ang II (angiotensin II) to induce fibrosis in HCFs (human corneal fibroblasts) and MCF (Michigan Cancer Foundation, MCF) cells in vitro, the miRNA-seq results of previous studies were validated. Proliferative and invasive ability of HCFs and MCFs was detected by Cell Counting Kit-8 assay (CCK-8) and scratch experiment after overexpressing miR-135a in HCFs and MCF cells. Protein and mRNA expression was tested using Western blot and qPCR. The target of miR-135a was verified as SIRT1 by a luciferase reporter assay and the activities of the mitochondrial respiratory enzyme complexes I, II, III, and IV were determined colorimetrically. The activities of malondialdehyde, reactive oxygen species, and superoxide dismutase in cells were detected with enzyme-linked immunosorbent assay (ELISA).
Results:
miR-135a expression was elevated in HCFs and MCFs cells in the Ang II group than control group. Overexpression of miR-135a could promote the proliferation, migration, oxidative stress, as well as fibrosis of cardiac fibroblasts and suppresses mitochondrial activity. In addition, we found SIRT1 was a target gene of miR-135a. What is more, the findings showed miR-135a promoted fibrosis in HCFs and MCFs cells acting through regulation of SIRT1.
Conclusions:
miR-135a mediates mitochondrial oxidative respiratory function through SIRT1 to regulate atrial fibrosis.
Insights
MicroRNA-135a promotes atrial fibrosis by suppressing mitochondrial activity and regulating sirtuin 1 (SIRT1) in cardiac fibroblasts. This study reveals a novel mechanism linking miR-135a, SIRT1, and mitochondrial function in fibrosis progression.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
- Fibrosis Research
Background:
- Atrial fibrosis is a key factor in atrial fibrillation.
- The role of microRNAs in cardiac fibroblast regulation is increasingly recognized.
- Mitochondrial dysfunction is implicated in fibrotic processes.
Purpose of the Study:
- To investigate the function of microRNA-135a (miR-135a) in atrial fibrosis.
- To elucidate the mechanism involving miR-135a and sirtuin 1 (SIRT1) in cardiac fibroblasts.
- To understand the regulation of atrial fibrosis via mitochondrial oxidative respiration.
Main Methods:
- Induction of fibrosis in human and mouse cardiac fibroblasts using Angiotensin II (Ang II).
- Assessment of cell proliferation, migration, and fibrosis markers.
- Validation of miR-135a targeting of SIRT1 using luciferase reporter assays.
- Measurement of mitochondrial respiratory enzyme activity and oxidative stress markers.
Main Results:
- miR-135a expression was upregulated in fibrotic cardiac fibroblasts.
- Overexpression of miR-135a enhanced fibroblast proliferation, migration, oxidative stress, and fibrosis.
- miR-135a was confirmed to target SIRT1, and its overexpression suppressed mitochondrial activity.
- miR-135a promoted fibrosis by regulating SIRT1 and impacting mitochondrial function.
Conclusions:
- miR-135a plays a significant role in promoting atrial fibrosis.
- The miR-135a/SIRT1 axis regulates mitochondrial oxidative respiratory function.
- Targeting miR-135a may offer a therapeutic strategy for atrial fibrosis.
