Rho kinase signaling pathway mediates high uric acid-induced oxidative damage and apoptosis of renal tubular cells by regulating mitochondrial dynamin and biosynthesis related genes
LI Jiachang
MA Yuhan
WEI Jiali
Abstract：Objective To explore the related mechanisms of oxidative damage and apoptosis of renal tubules in hyperuricemia mediated by the Rho kinase signaling pathway via the mitochondrial pathway.Methods Human renal tubular epithelial cells(HK-2 cells)were divided into 6 groups:NC group(normal control),transforming growth factor-β1(TGF-β1)group,uric acid group(intervention with high uric acid stimulation),fasudil group[receiving Rho-associated protein kinase(ROCK)inhibitor],ROCK1 siRNA group(intervention with ROCK1 gene silencing),sc-siRNA group(negative control).The expression levels of mitochondrial-related proteins in the cells of each group were detected by using Western blot and quantitative real-time polymerase chain reaction(qRT-PCR),and the expression levels were compared among different groups.Results High uric acid significantly upregulated the expression of myosin phosphatase-targeting subunit 1(MYPT1)in HK-2 cells,suggesting an increase in Rho kinase activity.High uric acid upregulated the expression level of manganese superoxide dismutase 2(MnSOD2)mRNA in HK-2 cells,while the pretreatment with fasudil significantly inhibited this change.After transfection with ROCK1 siRNA,the expression level of MnSOD2 mRNA in HK-2 cells was significantly decreased.The regulations of mitochondrial dynamin and biosynthesis genes via the Rho kinase pathway also affected the apoptosis process of the cells.Conclusion Rho kinase may accelerate the progression of hyperuricemic nephropathy by regulating mitochondrial oxidative damage and apoptosis.
Keywords：Rho kinaseHyperuricemic nephropathyMitochondrial pathwayOxidative damageApoptosis
Publication Date：2025-12-30
Online Publishing Date：2026-01-16(First online date of this platform, not the publication date of the document)
Pages：6( 1336-1341 )