TTC36 Involved In The Injury Of Renal Proximal Tubular Epithelial Cell By Regulating Inflammation

Renal tubular epithelial cells(TECs)are assailable and are the main victims of kidney damage.TECs could exhibit immune response and secrete inflammatory mediators.Inflammatory response and mitochondrial dysfunction are typical manifestations of kidney damage.Tetratricopeptide repeat domain 36(TTC36)is specifically expressed in renal proximal tubules within the kidney,however,its function in kidney remains unknown.In this study,we first explored the function of TTC36 in renal proximal tubular epithelial cells HK-2.Overexpression of TTC36 significantly suppressed the expression of inflammatory mediators.Meanwhile,TTC36 overexpression also reduced apoptosis,promoted proliferation,and strengthened tight junction.Furthermore,TTC36 overexpression could mitigate mitochondrial dysfunction induced by cisplatin,including maintaining mitochondrial membrane potential and ensuring the gene expressions related to mitochondrial fusion,activation of mitophagy,and mitochondrial safeguard.Further studies showed that overexpression of TTC36 could up-regulate the expression of IκBα,prolong the half-life of IκBα,affect the degradation of IκBα mediated by the proteasome,and thereby inhibit the activation of NF-κBp65.What is more,knocking down TTC36 on the basis of its overexpression reduced the expression of IκBα and increased the expression of inflammatory mediators.Knocking down IκBα on the basis of overexpression TTC36 increased the expressions of inflammatory mediator and pro-apoptotic proteins and reduced the expression of anti-apoptotic proteins.Moreover,TTC36 was down-regulated and negatively related to renal damage in mice kidneys with AKI.In conclusion,TTC36 may inhibit the NF-κB p65 pathway by enhancing the expression of IκBα to mitigate inflammatory reaction,thereby reducing cell damage,inhibiting apoptosis,promoting proliferation,maintaining tight junctions,and maintaining mitochondrial homeostasis in HK-2 cells.These results indicate the protective effects of TTC36 on the kidney and provide a possible therapeutic target for kidney injury.