The role of thrombospondin-1-mediated TGF-b1 on collagen type III synthesis induced by high glucose Mengxiong Tang • Fenghua Zhou • Wei Zhang • Zhongxiu Guo • Yuanyuan Shang • Huixia Lu • Ruijuan Lu • Yun Zhang • Yuguo Chen • Ming Zhong Received: 7 July 2010 / Accepted: 28 August 2010 / Published online: 28 September 2010 Ó Springer Science+Business Media, LLC. 2010 Abstract Transforming growth factor-b1 (TGF-b1) has been thought to play a major role during cardiac fibrosis in the development of diabetic cardiomyopathy, and cardiac fibrosis mainly as a result of an increase of collagen type III occurs in the human hearts with diabetes. Thrombospon- din-1 (TSP-1) has been reported to activate the latent complex of TGF-b1. We examined the effects of TSP-1 on the expression of TGF-b1 and collagen type III by rat cardiac fibroblasts in high ambient glucose. We demon- strated that high glucose induces the mRNA and protein expression of collagen type III, TGF-b1, and TSP-1. Fur- thermore, the mRNA and protein expression of collagen type III induced by high glucose was downregulated after treatment with TGF-b1 antibody, or TSP-1 siRNA. The expression of TGF-b1 increased by high glucose was also reversed after treatment with TSP-1 siRNA. Our findings suggest that the TSP-1 participates in the upregulation of TGF-b1, collagen type III by high glucose and may provide new therapeutic strategies for diabetic cardiomyopathy. Keywords Thrombospondin-1 Á Transforming growth factor-b1 Á Collagen type III Á Cardiac fibroblasts Abbreviations TSP-1 Thrombospondin-1 TGF-b1 Transforming growth factor-b1 Introduction Diabetic cardiomyopathy is one of the leading causes of increased morbidity and mortality in patients with type 1 and 2 diabetes [1–3]. Interstitial fibrosis is a major factor underlying the myocardial hypertrophy and diastolic dys- function that characterize diabetic cardiomyopathy [2, 4, 5]. The degree of hyperglycemia may promote the pro- gression of heart failure mainly by excessive interstitial myocardial collagen accumulation, which could result in impaired diastolic and systolic function [6, 7]. The com- position of ECM, a complex network of structural proteins, mainly collagen type I and III in the myocardium, provides architectural support for the myocardium and plays an important role in myocardial function [8]. In the hearts of patients with diabetes, collagen remodeling mainly as a result of an increase in collagen type III occurs in the perimysium and perivascular region [9]. Several studies have demonstrated an accumulation of collagens including collagen type III in diabetic cardiomyopathy, which has been related to left-ventricular diastolic and systolic dys- function [10, 11]. It has been shown that transforming growth factor-b1 (TGF-b1) plays a role in cell growth, differentiation, apop- tosis, inflammatory processes, and gene expression [12, 13]. M. Tang Á F. Zhou Á W. Zhang Á Z. Guo Á Y. Shang Á H. Lu Á R. Lu Á Y. Zhang Á Y. Chen (&) Á M. Zhong (&) Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, People’s Republic of China e-mail: yuguochenjn@yahoo.cn M. Zhong e-mail: zhongmingjn@yahoo.cn M. Tang Á R. Lu Á Y. Chen Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China F. Zhou Á W. Zhang Á Z. Guo Á Y. Shang Á H. Lu Á Y. Zhang Á M. Zhong Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China 123 Mol Cell Biochem (2011) 346:49–56 DOI 10.1007/s11010-010-0590-7