Naringenin inhibits transforming growth factor‑β1‑induced cardiac fibroblast proliferation and collagen synthesis via G0/G1 arrest

Liu,Mingxin; Xu,Xiping; Zhao,Jianhua; Tang,Yanhong

doi:10.3892/etm.2017.5103

Naringenin inhibits transforming growth factor‑β1‑induced cardiac fibroblast proliferation and collagen synthesis via G0/G1 arrest

Authors:
- Mingxin Liu
- Xiping Xu
- Jianhua Zhao
- Yanhong Tang
View Affiliations

Affiliations: Department of Cardiology, The First People's Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: September 5, 2017 https://doi.org/10.3892/etm.2017.5103
Pages: 4425-4430

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The Traditional Chinese Medicine naringenin (NRG) has a number of biological effects, including anti‑inflammatory, anti‑oxidative, anti‑tumor and anti‑atherosclerotic effects. However, the mechanism underlying its effects remains unclear. The aim of the present study is to investigate the role and mechanism of NRG on proliferation and collagen synthesis of cardiac fibroblasts (CFs) induced by transforming growth factor β1 (TGF‑β1). Firstly, proliferation and collagen synthesis in CFs subjected to TGF‑β1 was assessed subsequent to the consumption of NRG or control treatment. Additionally, the cell cycle of different groups and the roles of cyclins and cyclin‑dependent kinases (CDKs) in NRG treatment of CFs were detected. In the present study, it was revealed that treatment of CFs with NRG resulted in attenuated fibroblast α‑smooth muscle actin expression, deceased proliferation and collagen synthesis when compared with a TGF‑β1 stimulus. Additionally, it was demonstrated that cell population of CFs treated with NRG in the S‑phase became smaller whereas that of CFs in the G0/G1‑phase increased when compared with the TGF‑β1 group. Mechanistically, the expression of cyclin D1‑CDK4/6 and cyclin E2‑CDK2 were inhibited in the NRG treatment group. These results illustrated that the protective effects of NRG on proliferation and collagen synthesis of CFs were at least in part due to G0/G1 arrest. Therefore, NRG may become a novel strategy for treating cardiac fibrosis in the future.

View Figures

View References

1	Yi X, Li X, Zhou Y, Ren S, Wan W, Feng G and Jiang X: Hepatocyte growth factor regulates the TGF-β1-induced proliferation, differentiation and secretory function of cardiac fibroblasts. Int J Mol Med. 34:381–390. 2014.PubMed/NCBI
2	Zhou Y, Yi X, Wang T and Li M: Effects of angiotensin II on transient receptor potential melastatin 7 channel function in cardiac fibroblasts. Exp Ther Med. 9:2008–2012. 2015. View Article : Google Scholar : PubMed/NCBI
3	Li M, Yi X, Ma L and Zhou Y: Hepatocyte growth factor and basic fibroblast growth factor regulate atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease via the mitogen-activated protein kinase signaling pathway. Exp Ther Med. 6:1121–1126. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zhou YM, Li MJ, Zhou YL, Ma LL and Yi X: Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease. Int J Clin Exp Med. 8:21201–21207. 2015.PubMed/NCBI
5	Stempien-Otero A, Kim DH and Davis J: Molecular networks underlying myofibroblast fate and fibrosis. J Mol Cell Cardiol. 97:153–161. 2016. View Article : Google Scholar : PubMed/NCBI
6	Travers JG, Kamal FA, Robbins J, Yutzey KE and Blaxall BC: Cardiac fibrosis: The fibroblast awakens. Circ Res. 118:1021–1040. 2016. View Article : Google Scholar : PubMed/NCBI
7	Moore-Morris T, Cattaneo P, Puceat M and Evans SM: Origins of cardiac fibroblasts. J Mol Cell Cardiol. 91:1–5. 2016. View Article : Google Scholar : PubMed/NCBI
8	van Putten S, Shafieyan Y and Hinz B: Mechanical control of cardiac myofibroblasts. J Mol Cell Cardiol. 93:133–142. 2016. View Article : Google Scholar : PubMed/NCBI
9	Pinho-Ribeiro FA, Zarpelon AC, Mizokami SS, Borghi SM, Bordignon J, Silva RL, Cunha TM, Alves-Filho JC, Cunha FQ, Casagrande R and Verri WA Jr: The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-κB activation. J Nutr Biochem. 33:8–14. 2016. View Article : Google Scholar : PubMed/NCBI
10	Xing BH, Yang FZ and Wu XH: Naringenin enhances the efficacy of human embryonic stem cell-derived pancreatic endoderm in treating gestational diabetes mellitus mice. J Pharmacol Sci. 131:93–100. 2016. View Article : Google Scholar : PubMed/NCBI
11	Zhang F, Dong W, Zeng W, Zhang L, Zhang C, Qiu Y, Wang L, Yin X, Zhang C and Liang W: Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation. Breast Cancer Res. 18:382016. View Article : Google Scholar : PubMed/NCBI
12	Zhang N, Yang Z, Yuan Y, Li F, Liu Y, Ma Z, Liao H, Bian Z, Zhang Y, Zhou H, et al: Naringenin attenuates pressure overload-induced cardiac hypertrophy. Exp Ther Med. 10:2206–2212. 2015. View Article : Google Scholar : PubMed/NCBI
13	Chtourou Y, Slima AB, Makni M, Gdoura R and Fetoui H: Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats. Pharmacol Rep. 67:1090–1097. 2015. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Roche P and Czubryt MP: Transcriptional control of collagen I gene expression. Cardiovasc Hematol Disord Drug Targets. 14:107–120. 2014. View Article : Google Scholar : PubMed/NCBI
16	Li AH, Liu PP, Villarreal FJ and Garcia RA: Dynamic changes in myocardial matrix and relevance to disease: Translational perspectives. Circ Res. 114:916–927. 2014. View Article : Google Scholar : PubMed/NCBI
17	Langan TJ and Chou RC: Synchronization of mammalian cell cultures by serum deprivation. Methods Mol Biol. 761:75–83. 2011. View Article : Google Scholar : PubMed/NCBI
18	Lin X, Yang X, Li Q, Ma Y, Cui S, He D, Lin X, Schwartz RJ and Chang J: Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway. Mol Cell Biol. 32:297–308. 2012. View Article : Google Scholar : PubMed/NCBI
19	Lundberg AS and Weinberg RA: Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 18:753–761. 1998. View Article : Google Scholar : PubMed/NCBI
20	Lauper N, Beck AR, Cariou S, Richman L, Hofmann K, Reith W, Slingerland JM and Amati B: Cyclin E2: A novel CDK2 partner in the late G1 and S phases of the mammalian cell cycle. Oncogene. 17:2637–2643. 1998. View Article : Google Scholar : PubMed/NCBI
21	Lee JJ, Yi H, Kim IS, Nhiem NX, Kim YH and Myung CS: (2S)-naringenin from Typha angustata inhibits vascular smooth muscle cell proliferation via a G0/G1 arrest. J Ethnopharmacol. 139:873–878. 2012. View Article : Google Scholar : PubMed/NCBI
22	Bendris N, Lemmers B and Blanchard JM: Cell cycle, cytoskeleton dynamics and beyond: The many functions of cyclins and CDK inhibitors. Cell Cycle. 14:1786–1798. 2015. View Article : Google Scholar : PubMed/NCBI