Mechanisms of Bradykinin-Induced Expression of Connective Tissue Growth Factor and Nephrin in Podocytes.

Mechanisms of Bradykinin-Induced Expression of Connective Tissue Growth Factor and Nephrin in Podocytes. Am J Physiol Renal Physiol. 2015 Oct 7;:ajprenal.00233.2015 Authors: Abou Msallem JP, Chalhoub H, Al Hariri M, Saad L, Jaffa M, Ziyadeh F, Jaffa AA Abstract Diabetic Nephropathy (DN) is the main cause of morbidity and mortality in diabetes, characterized by mesangial matrix deposition and podocytopathy including podocyte loss. The risk factors and mechanisms involved in the pathogenesis of DN are still not completely defined. In the current study we aim to understand the cellular mechanisms through which activation of B2 kinin receptors contribute to the initiation and progression of DN. Stimulation of cultured rat podocytes with bradykinin (BK) resulted in a significant increase in reactive oxygen species generation (ROS) and this was associated with a significant increase in NOX1 and NOX4 protein and mRNA levels. BK stimulation also resulted in a signicant increase in the phosphorylation of ERK1/2 and Akt and this effect was inhibited in the presence of NOX1 and Nox4 siRNA. Furthermore podocytes stimulated with BK resulted in a significant increase in the protein and mRNA levels of connective tissue growth factor (CTGF) and at the same time a significant decrease in the protein and mRNA levels of nephrin. siRNA targeted against NOX1 and NOX4 significantly inhibited the BK-induced increase in CTGF. Nephrin expression was increase...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research