Role of PKC and TGF-beta receptor in glucose-induced proliferation of smooth muscle cells

The role of protein kinase C (PKC) and transforming growth factor (TGF)-bet a in the proliferation of vascular smooth muscle cells (SMCs) under a high glucose condition was investigated. [H-3]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM gl ucose, and this increase was inhibited by an anti-TGF-beta antibody or a PK C-beta specific inhibitor, LY333531. The amount of active and total TGF-bet a1 in the conditioned media did not differ between 5.5 and 20 mM glucose. H owever, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not. This increased expression of the TGF-beta receptor type II was prevented b y LY333531. These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the acce lerated proliferation of SMCs under a high glucose condition, leading to th e development of diabetic macroangiopathy. (C) 2001 Academic Press.