Abnormal Downregulation of Caveolin-3 Mediates the Pro-Fibrotic Action of MicroRNA-22 in a Model of Myocardial Infarction

Feb 28, 2018Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

Lowered Caveolin-3 Levels May Help MicroRNA-22 Promote Heart Scarring After a Heart Attack

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Cav3 depletion in cardiac fibroblasts induced a significant increase in collagen content and cell proliferation.

Decreased Cav3 expression is associated with cardiac fibrosis in both animal and cell models.
Cav3 overexpression inhibits collagen deposition caused by angiotensin II through the inactivation of protein kinase C (PKC)ε.
miR-22 is confirmed as a direct target of Cav3 and is significantly upregulated in the ischemic border zone after myocardial infarction.
Increased miR-22 levels in cardiac fibroblasts lead to enhanced cell proliferation and elevated collagen and α-smooth muscle actin levels.
The knockdown of endogenous miR-22 reduces the number of cardiac fibroblasts.

AI simplified

BACKGROUND/AIMS: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms.

METHODS: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model. To investigate the role of Cav3 in cardiac fibrosis, we transfected cardiac fibroblasts (CFs) with the siRNA of Cav3 and Cav3-overexpressing plasmid. The collagen content and proliferation of CFs were detected by qRT-PCR, western blot, MTT, and immunofluorescence. A luciferase reporter gene assay and gain/loss of function were used to detect the relationship between miR-22 and Cav3.

RESULTS: Cav3 depletion in CFs induced an increase in collagen content, cell proliferation, and phenotypic conversion of fibroblasts to myofibroblasts. Conversely, Cav3 overexpression in CFs was shown to inhibit angiotensin II-mediated excessive collagen deposition through protein kinase C (PKC)ε inactivation. Cav3 was experimentally confirmed as a direct target of miR-22, containing two seed binding sites in its 3'-untranslated region, and miR-22 was demonstrated to be significantly upregulated in the ischemic border zone in mice after myocardial infarction and in neonatal rat CFs pretreated with angiotensin II. miR-22 overexpression increased CFs proliferation, and collagen and α-smooth muscle actin levels in CFs, while the knockdown of endogenous miR-22 decreased CFs numbers.

CONCLUSIONS: Our findings demonstrate that miR-22 accelerates cardiac fibrosis through the miR-22-Cav3-PKCε pathway, which, therefore, may represent a new therapeutic target for treatment of excessive fibrosis-associated cardiac diseases.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text ↗

Abnormal Downregulation of Caveolin-3 Mediates the Pro-Fibrotic Action of MicroRNA-22 in a Model of Myocardial Infarction

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief