SMOC1 silencing suppresses the angiotensin II‑induced myocardial fibrosis of mouse myocardial fibroblasts via affecting the BMP2/Smad pathway

Wang,Yize; Wu,Xianming

doi:10.3892/ol.2018.8989

SMOC1 silencing suppresses the angiotensin II‑induced myocardial fibrosis of mouse myocardial fibroblasts via affecting the BMP2/Smad pathway

Authors:
- Yize Wang
- Xianming Wu
View Affiliations

Affiliations: Department of Cardiology, Yiyang Central Hospital, Yiyang, Hunan 413000, P.R. China
Published online on: June 19, 2018 https://doi.org/10.3892/ol.2018.8989
Pages: 2903-2910
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

SPARC‑related modular calcium binding 1 (SMOC1) represents a vital member of the SPARC matricellular protein family that regulates cell matrix interaction through binding to cell‑surface receptors. The present study aimed to investigate the roles and molecular mechanisms of SMOC1 silencing on the fibrosis of myocardial fibroblasts (MFBs). Cell Counting kit‑8 and flow cytometry assays were performed to determine cell viability and reactive oxygen species (ROS) content, respectively. ELISA was performed to detect the expression of associated cytokines and matrix proteins. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction assays were used to evaluate the expression of associated proteins and mRNAs, respectively. The results revealed that SMOC1 silencing suppressed the cell viability of angiotensin II (Ang II)‑treated MFBs. SMOC1 silencing reduced the ROS content and oxidative stress in MFBs in response to Ang II. Furthermore, SMOC1 silencing downregulated the expression levels of fibrosis‑associated proteins in Ang II‑treated MFBs. SMOC1 silencing affected the bone morphogenetic protein 2 (BMP2)/Smad signaling pathway in Ang II‑treated MFBs. In conclusion, the results of the present study suggested that SMOC1 silencing suppressed the Ang II‑induced myocardial fibrosis of mouse MFBs through affecting the BMP2/Smad signaling pathway.

View Figures

View References

1	GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 390:1211–1259. 2017. View Article : Google Scholar : PubMed/NCBI
2	Dunlay SM and Roger VL: Understanding the epidemic of heart failure: Past, present, and future. Curr Heart Fail Rep. 11:404–415. 2014. View Article : Google Scholar : PubMed/NCBI
3	Lebrin F, Goumans MJ, Jonker L, Carvalho RL, Valdimarsdottir G, Thorikay M, Mummery C, Arthur HM and ten Dijke P: Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. Embo J. 23:4018–4028. 2004. View Article : Google Scholar : PubMed/NCBI
4	McCain ML, Agarwal A, Nesmith HW, Nesmith AP and Parker KK: Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues. Biomaterials. 35:5462–5471. 2014. View Article : Google Scholar : PubMed/NCBI
5	Daniels A, van Bilsen M, Goldschmeding R, van der Vusse GJ and van Nieuwenhoven FA: Connective tissue growth factor and cardiac fibrosis. Acta Physiol. 195:321–338. 2009. View Article : Google Scholar
6	Fan D, Takawale A, Lee J and Kassiri Z: Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenesis Tissue Repair. 5:152012. View Article : Google Scholar : PubMed/NCBI
7	Segura AM, Frazier OH and Buja LM: Fibrosis and heart failure. Heart Fail Rev. 19:173–185. 2014. View Article : Google Scholar : PubMed/NCBI
8	Fan D, Takawale A, Basu R, Patel V, Lee J, Kandalam V, Wang X, Oudit GY and Kassiri Z: Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction. Cardiovasc Res. 103:268–280. 2014. View Article : Google Scholar : PubMed/NCBI
9	Ma Y, Halade GV and Lindsey ML: Extracellular matrix and fibroblast communication following myocardial infarction. J Cardiovasc Transl Res. 5:848–857. 2012. View Article : Google Scholar : PubMed/NCBI
10	Yang YL, Liu YS, Chuang LY, Guh JY, Lee TC, Liao TN, Hung MY and Chiang TA: Bone morphogenetic protein-2 antagonizes renal interstitial fibrosis by promoting catabolism of type I transforming growth factor-beta receptors. Endocrinology. 150:727–740. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zeisberg M, Bottiglio C, Kumar N, Maeshima Y, Strutz F, Muller GA and Kalluri R: Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am J Physiol Renal Physiol. 285:F1060–F1067. 2003. View Article : Google Scholar : PubMed/NCBI
12	Yang YL, Ju HZ, Liu SF, Lee TC, Shih YW, Chuang LY, Guh JY, Yang YY, Liao TN, Hung TJ and Hung MY: BMP-2 suppresses renal interstitial fibrosis by regulating epithelial-mesenchymal transition. J Cell Biochem. 112:2558–2565. 2011. View Article : Google Scholar : PubMed/NCBI
13	Wang S, Sun A, Li L, Zhao G, Jia J, Wang K, Ge J and Zou Y: Up-regulation of BMP-2 antagonizes TGF-β1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex. J Cell Mol Med. 16:2301–2310. 2012. View Article : Google Scholar : PubMed/NCBI
14	Flanders KC: Smad3 as a mediator of the fibrotic response. Int J Exp Pathol. 85:47–64. 2004. View Article : Google Scholar : PubMed/NCBI
15	Kim KK, Wei Y, Szekeres C, Kugler MC, Wolters PJ, Hill ML, Frank JA, Brumwell AN, Wheeler SE, Kreidberg JA and Chapman HA: Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. J Clin Invest. 119:213–224. 2009.PubMed/NCBI
16	Lan HY: Diverse roles of TGF-beta/Smads in renal fibrosis and inflammation. Int J Biol Sci. 7:1056–1067. 2011. View Article : Google Scholar : PubMed/NCBI
17	Bornstein P and Sage EH: Matricellular proteins: Extracellular modulators of cell function. Curr Opin Cell Biol. 14:608–616. 2002. View Article : Google Scholar : PubMed/NCBI
18	Vannahme C, Smyth N, Miosge N, Gosling S, Frie C, Paulsson M, Maurer P and Hartmann U: Characterization of SMOC-1, a novel modular calcium-binding protein in basement membranes. J Biol Chem. 277:37977–37986. 2002. View Article : Google Scholar : PubMed/NCBI
19	Gersdorff N, Müller M, Schall A and Miosge N: Secreted modular calcium-binding protein-1 localization during mouse embryogenesis. Histochem Cell Biol. 126:705–712. 2006. View Article : Google Scholar : PubMed/NCBI
20	Thomas JT, Canelos P, Luyten FP and Moos M Jr: Xenopus SMOC-1 Inhibits bone morphogenetic protein signaling downstream of receptor binding and is essential for postgastrulation development in Xenopus. J Biol Chem. 284:18994–19005. 2009. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Phillips MI and Kagiyama S: Angiotensin II as a pro-inflammatory mediator. Curr Opin Investig Drugs. 3:569–577. 2002.PubMed/NCBI
23	Marshall RP, McAnulty RJ and Laurent GJ: Angiotensin II is mitogenic for human lung fibroblasts via activation of the type 1 receptor. Am J Respir Crit Care Med. 161:1999–2004. 2000. View Article : Google Scholar : PubMed/NCBI
24	Uhal BD, Kim JK, Li X and Molina-Molina M: Angiotensin-TGF-beta 1 crosstalk in human idiopathic pulmonary fibrosis: Autocrine mechanisms in myofibroblasts and macrophages. Curr Pharm Des. 13:1247–1256. 2007. View Article : Google Scholar : PubMed/NCBI
25	Zhu M, Chen D, Li D, Ding H, Zhang T, Xu T and Zhang Y: Luteolin inhibits angiotensin II-induced human umbilical vein endothelial cell proliferation and migration through downregulation of Src and Akt phosphorylation. Circ J. 77:772–779. 2013. View Article : Google Scholar : PubMed/NCBI
26	Rosin NL, Sopel M, Falkenham A, Myers TL and Legare JF: Myocardial migration by fibroblast progenitor cells is blood pressure dependent in a model of angII myocardial fibrosis. Hypertens Res. 35:449–456. 2012. View Article : Google Scholar : PubMed/NCBI
27	Yang L, Zhu QJ, Zhou W, Ye J, Qian W, Zhu R, Hu TH and Hou XH: Effect of beta-elemene on the proliferation, migration and RhoA expression of hepatic stellate cells induced by angiotensin II. Zhonghua Gan Zang Bing Za Zhi. 16:748–751. 2008.(In Chinese). PubMed/NCBI
28	Bradshaw AD: Diverse biological functions of the SPARC family of proteins. Int J Biochem Cell Biol. 44:480–488. 2012. View Article : Google Scholar : PubMed/NCBI
29	Choi YA, Lim J, Kim KM, Acharya B, Cho JY, Bae YC, Shin HI, Kim SY and Park EK: Secretome analysis of human BMSCs and identification of SMOC1 as an important ECM protein in osteoblast differentiation. J Proteome Res. 9:2946–2956. 2010. View Article : Google Scholar : PubMed/NCBI
30	Boon K, Edwards JB, Eberhart CG and Riggins GJ: Identification of astrocytoma associated genes including cell surface markers. BMC Cancer. 4:392004. View Article : Google Scholar : PubMed/NCBI
31	Brellier F, Ruggiero S, Zwolanek D, Martina E, Hess D, Brown-Luedi M, Hartmann U, Koch M, Merlo A, Lino M and Chiquet-Ehrismann R: SMOC1 is a tenascin-C interacting protein over-expressed in brain tumors. Matrix Biol. 30:225–233. 2011. View Article : Google Scholar : PubMed/NCBI
32	Schieber M and Chandel NS: ROS function in redox signaling and oxidative stress. Curr Biol. 24:R453–462. 2014. View Article : Google Scholar : PubMed/NCBI
33	Kliment CR, Englert JM, Gochuico BR, Yu G, Kaminski N, Rosas I and Oury TD: Oxidative stress alters syndecan-1 distribution in lungs with pulmonary fibrosis. J Biol Chem. 284:3537–3545. 2009. View Article : Google Scholar : PubMed/NCBI
34	Papaharalambus CA and Griendling KK: Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med. 17:48–54. 2007. View Article : Google Scholar : PubMed/NCBI
35	Montezano AC, Callera GE, Yogi A, He Y, Tostes RC, He G, Schiffrin EL and Touyz RM: Aldosterone and angiotensin II synergistically stimulate migration in vascular smooth muscle cells through c-Src-regulated redox-sensitive RhoA pathways. Arterioscler Thromb Vasc Biol. 28:1511–1518. 2008. View Article : Google Scholar : PubMed/NCBI
36	Sun B, Huo R, Sheng Y, Li Y, Xie X, Chen C, Liu HB, Li N, Li CB, Guo WT, et al: Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. Hypertension. 61:352–360. 2013. View Article : Google Scholar : PubMed/NCBI
37	Voloshenyuk TG, Landesman ES, Khoutorova E, Hart AD and Gardner JD: Induction of cardiac fibroblast lysyl oxidase by TGF-β1 requires PI3K/Akt, Smad3, and MAPK signaling. Cytokine. 55:90–97. 2011. View Article : Google Scholar : PubMed/NCBI
38	Wang B, Hao J, Jones SC, Yee MS, Roth JC and Dixon IM: Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Am J Physiol Heart Circ Physiol. 282:H1685–H1696. 2002. View Article : Google Scholar : PubMed/NCBI