Role of PI3K/Akt signal pathway on proliferation of mesangial cell induced by HMGB1

Mesangial cell (MC) proliferation is an important event in LN. Our previous studies have shown that extracellular High Mobility Group Box-1 protein (HMGB1) plays a critical role in pathophysiological mechanism of lupus nephritis (LN) and HMGB1 could induce MC proliferation. The purpose of this study is to investigate the effect of phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway activation on mesangial cell proliferation induced by HMGB1 and whether Toll-like receptor 2 (TLR2) plays an important role in this progress. The results showed that HMGB1 induced overexpression of p85, p110 and p-Akt in mouse mesangial cell (MMC) and increased the proliferative level of MMC cells. In addition, HMGB1 induced a physical interaction between TLR2 and p85. The TLR2 neutralization antibody and LY294002 both reduced the MMC proliferation levels induced by HMGB1 and also blocked the HMGB1-dependent phosphorylation of the Akt. Thus, HMGB1 increases interaction between TLR2 with p85 and in sequence phosphorylates Akt at ser473, thereafter mediates MMC proliferation, which contributed significantly to the pathophysiology of MMCs dysfunction. (C) 2016 Elsevier Ltd. All rights reserved.