Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways

Abstract

BackgroundMesangial proliferative glomerulonephritis (MsPGN) accounts for a main cause of chronic kidney disease (CKD), chronic renal failure and uremia. This paper aimed to examine the effect of Ntrk1 on MsPGN development, so as to identify a novel therapeutic target for MsPGN.MethodsThe MsPGN rat model was constructed by single injection of Thy1.1 monoclonal antibody via the tail vein. Additionally, the Ntrk1 knockdown rat model was established by injection of Ntrk1-RNAi lentivirus via the tail vein. Periodic acid-schiff staining and immunohistochemistry (IHC) were performed on kidney tissues. Moreover, the rat urinary protein was detected. Mesangial cells were transfected and treated with p38 inhibitor (SB202190) and ERK inhibitor (PD98059). Meanwhile, the viability and proliferation of mesangial cells were analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine assays. Gene expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot (WB) assays.ResultsThe proliferation of mesangial cells was enhanced in glomerulus and Ki67 expression was up-regulated in renal tubule of MsPGN rats. The urine protein level increased in MsPGN rats. Pro-inflammatory factors and Ntrk1 expression were up-regulated in glomerulus of MsPGN rats. Ntrk1 up-regulation promoted the viability, proliferation, expression of pro-inflammatory factors and activation of the STAT3, p38 and ERK signaling pathways in mesangial cells. Ntrk1 knockdown reduced mesangial cell proliferation, urine protein, pro-inflammatory factors, activation of STAT3, p38 and ERK signaling pathways in glomerulus, and decreased Ki67 expression in renal tubule of MsPGN rats. Treatment with SB202190 and PD98059 reversed the effect of Ntrk1 on promoting the viability, proliferation and inflammatory response of mesangial cells.ConclusionNtrk1 promoted mesangial cell proliferation and inflammation in MsPGN rats by activating the STAT3 and p38/ERK MAPK signaling pathways.