Upregulation of Fibronectin by Peroxynitrite in Mesangial Cell via the JAK/STAT Signaling Pathways

Abstract: Oxidative stress is one of the important underlying mechanism of diabetic nephropathy (DN) development and progression. Peroxynitrite (ONOO–) plays a very important role in the pathogenesis caused by oxidative stress and has been demonstrated to be involved in diabetes and its complications. In our study， we observed the effect of ONOO– on fibronectin (FN) generation in glomerular mesangial cells (MC) and explored its mechanism. The human glomerular mesangial cells (HMC) were divided into four groups: NG group， HG group， HG+UA group， and HG+AG490 group. Then， HMCs were harvested and the total protein was extracted at 12， 24， 48 h after stimulation; meanwhile， the medium was collected for detecting the protein level of FN by enzyme-linked immunosorbent assay (ELISA). The expression of NT total protein (a marker for ONOO–)， p-JAK2， p-STAT3 were examined by immunocytochemistry and Western blot. The results showed that in HG group， the content of FN and the expression of NT， p-JAK2， p-STAT3 all increased significantly compared with NG group at the corresponding time (P<0.05)， meanwhile， the above protein all increased in a time course manner and reached to highest level at 48 h after stimulation; in HG+UA group， the content of FN and the expression of NT， p-JAK2， p-STAT3 were lower than HG group (P<0.05); in HG+AG490 group， all above protein except NT decreased significantly compared with HG group (P<0.05)， there was no obvious difference of NT expression between HG+AG490 group and HG group (P>0.05). These demonstrated that the excessive of ONOO– in high glucose environment could upregulate FN generation in MC via JAK/STAT signaling pathways.

CSTR: 32200.14.cjcb.2012.03.0010