TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR AND FIBRONECTIN EXPRESSIONS IN AORTIC SMOOTH-MUSCLE CELLS IN DIABETIC RATS

Smooth muscle cells in arteries of diabetic rats and rabbits have uniq ue properties including the overexpression of platelet-derived growth factor (PDGF) beta-receptor compared with controls. Fibronectin, one o f the increased components of extracellular matrices in diabetic arter ies, 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 beta-receptor. Moreover, fibronectin synthesis is regulate d by transforming growth factor-beta (TGF-beta). In this study, we rep ort on the expression of TGF-beta receptors in diabetic smooth muscle cells, by immunohistochemistry, cross-linking of I-125-TGF-beta 1 to c ells and quantitative reverse transcription-polymerase chain reaction. We also report on the effects of TGF-beta 1 on fibronectin synthesis of diabetic smooth muscle cells by use of ELISA and immunoprecipitatio n, in order to clarify the role of TGF-beta-fibronectin pathway in for ming characteristic changes of diabetic smooth muscle cells. Cultured aortic smooth muscle cells of diabetic rats expressed TGF-beta 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 recept or did not differ between the two types of smooth muscle cells. These changes were accompanied by increased fibronectin synthesis in diabeti c smooth muscle cells in response to TGF-beta 1. Furthermore, protein expression of fibronectin, and mRNA and protein of TGF-beta type II re ceptor were increased in the diabetic aorta compared with the control aorta in vivo, implying the importance of the TGF-beta-fibronectin pat hway for the unique biology of smooth muscle cells in the diabetic art ery.