Celastrol-induced suppression of the MiR- 21/ERK signalling pathway attenuates cardiac fibrosis and dysfunction

Mian Cheng, Gang Wu, Yue Song, Lin Wang, Ling Tu, Lizhi Zhang, Cuntai Zhang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: 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.

Original languageEnglish (US)
Pages (from-to)1928-1938
Number of pages11
JournalCellular Physiology and Biochemistry
Volume38
Issue number5
DOIs
StatePublished - 2016

Fingerprint

MAP Kinase Signaling System
Fibrosis
Fibroblasts
Transforming Growth Factor beta
Constriction
Collagen
East Asian Traditional Medicine
Ventricular Myosins
Mitogen-Activated Protein Kinase 3
Myosin Heavy Chains
tripterine
Brain Natriuretic Peptide
Mitogen-Activated Protein Kinase 1
Cardiomegaly
Atrial Natriuretic Factor
Therapeutics
MicroRNAs
Smooth Muscle
Echocardiography
Actins

Keywords

  • Celastrol
  • ERK
  • Micro RNA-21
  • Myocardial fibrosis

ASJC Scopus subject areas

  • Physiology

Cite this

Celastrol-induced suppression of the MiR- 21/ERK signalling pathway attenuates cardiac fibrosis and dysfunction. / Cheng, Mian; Wu, Gang; Song, Yue; Wang, Lin; Tu, Ling; Zhang, Lizhi; Zhang, Cuntai.

In: Cellular Physiology and Biochemistry, Vol. 38, No. 5, 2016, p. 1928-1938.

Research output: Contribution to journalArticle

Cheng, Mian ; Wu, Gang ; Song, Yue ; Wang, Lin ; Tu, Ling ; Zhang, Lizhi ; Zhang, Cuntai. / Celastrol-induced suppression of the MiR- 21/ERK signalling pathway attenuates cardiac fibrosis and dysfunction. In: Cellular Physiology and Biochemistry. 2016 ; Vol. 38, No. 5. pp. 1928-1938.
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abstract = "Background: 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.",
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T1 - Celastrol-induced suppression of the MiR- 21/ERK signalling pathway attenuates cardiac fibrosis and dysfunction

AU - Cheng, Mian

AU - Wu, Gang

AU - Song, Yue

AU - Wang, Lin

AU - Tu, Ling

AU - Zhang, Lizhi

AU - Zhang, Cuntai

PY - 2016

Y1 - 2016

N2 - Background: 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.

AB - Background: 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.

KW - Celastrol

KW - ERK

KW - Micro RNA-21

KW - Myocardial fibrosis

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