The role of thrombospondin-1-mediated TGF-β1 on collagen type III synthesis induced by high glucose.
Transforming growth factor-β1 (TGF-β1) 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. Thrombospondin-1 (TSP-1) has been reported to activate the latent complex of TGF-β1. We examined the effects of TSP-1 on the expression of TGF-β1 and collagen type III by rat cardiac fibroblasts in high ambient glucose. We demonstrated that high glucose induces the mRNA and protein expression of collagen type III, TGF-β1, and TSP-1. Furthermore, the mRNA and protein expression of collagen type III induced by high glucose was downregulated after treatment with TGF-β1 antibody, or TSP-1 siRNA. The expression of TGF-β1 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-β1, collagen type III by high glucose and may provide new therapeutic strategies for diabetic cardiomyopathy.
Tang
Mengxiong
M
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, People's Republic of China.
Zhou
Fenghua
F
Zhang
Wei
W
Guo
Zhongxiu
Z
Shang
Yuanyuan
Y
Lu
Huixia
H
Lu
Ruijuan
R
Zhang
Yun
Y
Chen
Yuguo
Y
Zhong
Ming
M
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D024061:Collagen Type III / Q000096:biosynthesis*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000008:administration & dosage*; D008297:Male; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D024061:Collagen Type III; D017931:DNA Primers; D034741:RNA, Small Interfering; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D005947:Glucose