Transforming growth factor-β receptor and fibronectin expressions in aortic smooth muscle cells in diabetic rats

Abstract

We have previously reported that cultured aortic smooth muscle cells (SMC) and medial layers of arteries of diabetic rats and rabbits express more platelet-derived growth factor (PDGF) b -receptor than those of non-diabetic animals [1,2]. In addition, diabetic SMC grow much faster than control SMC specifically in reponse to A-B heterodimer and B-B homodimer of PDGF, suggesting that the overexpression of PDGF b -receptor in SMC is a causative element in the accelerated growth of diabetic SMC. In an in vivo study, SMC-dominant intimal thickening was enhanced in diabetic rabbits compared with non-diabetic rabbits at 2 weeks after balloon catheter injury of the carotid arterial wall [2]. Taken together, the above results suggest that the change in growth properties of SMC by the overexpression of PDGF b -receptor plays a Diabetologia (1997) 40: 383-391 Transforming growth factor-b receptor and fibronectin expressions in aortic smooth muscle cells in diabetic rats b -receptor compared with controls. Fibronectin, one of the increased components of extracellular matrices in diabetic arteries, plays an important role in the phenotypic change of smooth muscle cells from the contractile to the synthetic type with the expression of the PDGF b -receptor. Moreover, fibronectin synthesis is regulated by transforming growth factor-b (TGF-b). In this study, we report on the expression of TGF-b receptors in diabetic smooth muscle cells, by immunohistochemistry, cross-linking of 125 I-TGF-b1 to cells and quantitative reverse transcription-polymerase chain reaction. We also report on the effects of TGF-b1 on fibronectin synthesis of diabetic smooth muscle cells by use of ELISA and immunoprecipitation, in order to clarify the role of TGF-b-fibronectin pathway in forming characteristic changes of diabetic smooth muscle cells. Cultured aortic smooth muscle cells of diabetic rats expressed TGF-b type II receptor about 8.7 times that of controls at the protein level and 5.7 times at the mRNA level, whereas the expression of the type I receptor did not differ between the two types of smooth muscle cells. These changes were accompanied by increased fibronectin synthesis in diabetic smooth muscle cells in response to TGF-b1. Furthermore, protein expression of fibronectin, and mRNA and protein of TGF-b type II receptor were increased in the diabetic aorta compared with the control aorta in vivo, implying the importance of the TGF-b-fibronectin pathway for the unique biology of smooth muscle cells in the diabetic artery. [Diabetologia (1997) 40: 383-391]

Ameliorative effects of aminoguanidine on rat aorta in Streptozotocin-induced diabetes and evaluation of α-SMA expression

“…PDGF is powerful SMC mitogen resulting in SMC migration and proliferation (28, 33) and released from injured endothelial cells in diabetics (28). In previous studies, researchers have reported that arterial SMCs and medial layers of arteries of diabetic rats express more PDGF β-receptor than those of control rats (32,34,35). Poulter et al (36) and Askari et al (31) suggested that proliferation of SMCs in the tunica media caused a increase in collagen synthesis.…”

Antagonistic Effects of TNF-α on TGF-β Signaling Through Down-Regulation of TGF-β Receptor Type II in Human Dermal Fibroblasts

“…Several lines of evidence suggest that transcriptional repression of the T␤R gene may be a major mechanism in inactivating T␤R in tumor cells (46). In contrast, up-regulation of T␤R expression has been demonstrated in fibrotic diseases, such as SSc, localized scleroderma, hepatic fibrosis, idiopathic hypertrophic obstructive cardiomyopathy, and atherosclerosis (22,26,(47)(48)(49)(50). Upregulation of T␤R expression would result in the deposition of ECM components, which are the chief pathologic features of fibrotic disorders.…”

Enhanced Expression of Osteopontin in Human Diabetic Artery and Analysis of Its Functional Role in Accelerated Atherogenesis

“…18 For the identification of OPN, we used the anti-human OPN antibody (10A16, 5 g/mL) as well as the anti-rat OPN antibody (MPIIIB10, 1:250 dilution), which also cross-reacts with human OPN, according to the manufacturer's instructions. For the identification of SMCs, we used the anti-␣-smooth muscle actin antibody (1A4, 1:1000 dilution).…”