Souchinone Inhibits Mesangial Cell Fibrosis and Inflammatory Response Through TGF‐β1/Smad signaling and NLRP3 inflammasome pathway

Abstract

Mesangial proliferative glomerulonephritis is characterized by an increased number of mesangial cells in the glomeruli in the kidneys and damage to the glomeruli by activation of some growth factors (e.g., angiotensin II) and deposition of extracellular matrix proteins. However, the effect of sauchinone on mesangial proliferative glomerulonephritis is still unclear. In the present study, we investigated the protective effect of sauchinone against angiotensin II (AngII)‐induced proliferation and fibrosis in human renal mesangial cells. Thus, this study was investigated the inhibitory effect of sauchinone (0.1–1 μM) on AngII‐stimulated mesangial cells proliferation and fibrosis. Sauchinone, one of the active lignan isolated from Saururus chinensis, was reported to possess broad bioactivities, such as anti‐inflammatory, anti‐oxidant, anti‐tumor, anti‐apoptosis and anti‐obesity effects. In this study, thymidine incorporation under AngII was significantly accelerated, which was inhibited by sauchinone in a dose dependent manner. In migration assays, a significant reduction in wound surface was observed in pretreatment of sauchinone. Sauchinone induced down‐regulation of cyclins/CDKs and up‐regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, AngII enhanced expression of fibrosis biomarkers such as collagen IV and CTGF, which was markedly attenuated by sauchinone. Sauchinone decreased TGF‐β1 and Smad‐2/Smad‐4 expression, whereas increased Smad‐7 expression under AngII. Furthermore, sauchinone inhibited AngII‐induced inflammatory factors level as well as NF‐κB p65 translocation and ROS production. These results suggested that sauchinone may alleviate mesangial proliferation and inflammation possibly involved in renal fibrotic process, further mesangial proliferative glomerulonephritis through disturbing TGF‐β1/Smad signaling and NLRP3 inflammasome pathway. Thus, sauchinone might prove to be effective in the treatment of renal dysfunction leading to mesangial proliferative glomerulonephritis. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2017R1A5A2015805)(2018R1D1A1B07050720).