TTC36 Promotes Renal Tubular Injury Via TGF-β1-induced Epithelial-mesenchymal Transition In A Mouse Model Of Chronic Kidney Disease

Proximal tubular epithelial cells(PTECs)injury is a central event during the pathogenesis of chronic kidney disease(CKD).Deregulated repair processes of PTECs contributes to cellular epithelial-mesenchymal transition(EMT),which in turn aggravates the progression of CKD and kidney fibrosis.Here,we firstly reported the role of TTC36 in EMT regulation and the progression of renal fibrosis induced by unilateral ureteral obstruction(UUO).Specifically,we observed that the reduction of TTC36 is associated with tubular EMT induced by UUO;what’s more,ablation of TTC36 in mice kidney attenuated UUO-mediated tubular injury and subsequent EMT;consistently,the TGF-β1 activated SMAD3 signaling and EMT were augmented by TTC36 overexpression in TGF-β1-treated HK2 cells.Further,TTC36 promoted the protein expression of CEBPB,which is involved in the TGF-β/SMAD3 signaling regulation,and CEBPB silence rescued the exacerbated SMAD3 signaling and downstream gene response.Collectively,our results revealed that TTC36 deficiency plays a protective role in tubular injury and renal fibrosis induced by UUO and TTC36 elevated TGF-β/SMAD3 signaling by possibly effecting CEBPB,suggesting that TTC36 inhibition may be a potential strategy in the therapy of obstructive nephropathy.