Investigation on the Role of ROS in Integrin-Mediated Signaling of Progressive Glomerulonephritis

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In order to clarify the role of ROS in the integrin-dependent signaling involved in progressive glomerulonephritis (GN), we investigated the localization and function of NAD(P)H oxidase -derived ROS signaling using a model of experimental GN (WKY masugi GN) and cultured parietal epithelial cells(PEC). Glomerular and crescent expression of NAD(P)H and DHE was increased in parallel with PEC proliferation and matrix accumulation during the course of GN. Inhibition of ROS production with angiotensin receptor inhibitor (ARB) in this GN model revealed that NAD(P)H oxidase-derived ROS signaling play an important role in PEC proliferation, matrix remodeling and crescent formation in progressive GN. Immunofluorescent study with cultured PEC showed that other Nox proteins except Nox2 may play a role in NAD(P)H oxidase oxidase-derived ROS signaling seen in progressive GN and crescent formation. These results indicate that NAD(P)H oxidase-derived ROS signaling play a critical role in crescent formation in progressive GN. Further study is required for development of pharmacological tool to inhibit NAD(P)H oxidase-derived ROS signaling involved in progression of GN in human.