The role of PI3‐k/Akt signaling pathway in sublytic C5b‐9 complexes‐induced synthesis of thrombospondin‐1 (Tsp‐1), transforming growth factor‐β1 (TGF‐β1) and proliferation of glomerular mesangial cells (GMCs) including secretion of extracelluar matrix (ECM)

Abstract

Sublytic complement C5b‐9 complexes can cause many forms of immune‐mediated diseases. But the role and relative signal pathway of sublytic C5b‐9 on the pathologic changes of glomerular mesangial cells (GMCs) has not been demonstrated. In this study, we first explored the effects of sublytic C5b‐9 on the synthesis of thrombospondin‐1 (Tsp‐1) and transforming growth factor‐β1 (TGF‐β1) including proliferation of GMCs and secretion of extracelluar matrix (ECM) i.e. fibronectin (FN), and then ascertained the roles of phosphatidylinositol 3‐kinase (PI3‐k)/Akt signal pathway in these processes by using small hairpin RNAs (shRNA). The results showed that the expression of Tsp‐1, TGF‐β1, cyclin D2 and 3H‐thymidine into DNA as well as FN in the GMCs stimulated by sublytic C5b‐9 complexes could be increased, and the elevation of these parameters mentioned‐above was also markedly reduced in the GMCs transfected with PI3‐k and Akt shRNA expression vectors or LY294002 (PI3‐k inhibitor) respectively. These data indicate that sublytic C5b‐9 can induce the sythesis of Tsp‐1, TGF‐β1 and promote the proliferation of GMCs and secretion of FN, and PI3‐k/Akt signal pathway plays a partial role in these reactions mediated by sublytic C5b‐9 complexes at least.