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Updated: Mar 21, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Celastrol-Induced Suppression of the MiR-21/ERK Signalling Pathway Attenuates Cardiac Fibrosis and Dysfunction
Insights
Celastrol prevents cardiac fibrosis and dysfunction by inhibiting the miR-21/ERK signaling pathway. This traditional medicine offers a potential therapeutic strategy for myocardial remodeling and improving heart function.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Myocardial fibrosis leads to cardiac remodeling and dysfunction.
- Celastrol, a traditional oriental medicine, shows potential cardioprotective effects.
- The precise mechanisms underlying celastrol's cardioprotective actions remain unclear.
Purpose of the Study:
- To investigate celastrol's efficacy in preventing cardiac fibrosis and dysfunction.
- To elucidate the underlying molecular mechanisms of celastrol's effects.
- To explore the role of the miR-21/ERK signaling pathway in celastrol's cardioprotective actions.
Main Methods:
- Cardiac fibrosis was induced in mice via transverse aortic constriction (TAC).
- Histological, biochemical, and echocardiographic methods assessed cardiac hypertrophy, fibrosis, and function.
- Western blotting and qRT-PCR were used to measure TGF-β1, ERK1/2, and miR-21 levels in vivo and in vitro.
Main Results:
- Celastrol treatment significantly reduced collagen deposition, cardiac hypertrophy markers (α-SMA, ANP, BNP, β-MHC), and miR-21 expression in TAC mice.
- Celastrol attenuated cardiac dysfunction and fibroblast proliferation in vitro.
- Celastrol inhibited the miR-21/ERK signaling pathway, reducing TGF-β1-induced miR-21 upregulation and ERK phosphorylation.
Conclusions:
- Celastrol ameliorates myocardial fibrosis and cardiac dysfunction.
- The miR-21/ERK signaling pathway is implicated in celastrol's protective effects against cardiac fibrosis.
- Targeting the miR-21/ERK pathway represents a potential therapeutic strategy for myocardial fibrosis.
Unlabelled:
Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms.
Methods:
Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC) in mice. Cardiac hypertrophy and fibrosis were evaluated based on histological and biochemical measurements. Cardiac function was evaluated by echocardiography. The levels of transforming growth factor beta 1 (TGF-β1), extracellular signal regulated kinases 1/2 (ERK1/2) signalling were measured using Western blotting, while the expression of miR-21was analyzed by real-time qRT-PCR in vitro and in vivo. In vitro studies, cultured cardiac fibroblasts (CFs) were treated with TGF-β1 and transfected with microRNA-21(miR21).
Results:
Celastrol treatment reduced the increased collagen deposition and down-regulated α-smooth muscle actin (α-SMA), atrial natriuretic peptide (ANP), brain natriuretic peptides (BNP), beta-myosin heavy chain (β-MHC), miR-21 and p-ERK/ERK. Cardiac dysfunction was significantly attenuated by celastrol treatment in the TAC mice model. Celastrol treatment reduced myocardial fibroblast viability and collagen content and down-regulated α-SMA in cultured CFs in vitro. Celastrol also inhibited the miR-21/ERK signalling pathway. Celastrol attenuated miR-21 up-regulation by TGF-β1 and decreased elevated p-ERK/ERK levels in CFs transfected with miR-21.
Conclusion:
MiR-21/ERK signalling could be a potential therapeutic pathway for the prevention of myocardial fibrosis. Celastrol ameliorates myocardial fibrosis and cardiac dysfunction, these probably related to miR-21/ERK signaling pathways in vitro and in vivo.
