#5453 LIPID NEPHROTOXICITY INDUCED BY HIF-1α ACTIVATION ACCELERATES INTERSTITIAL INJURY IN DIABETIC NEPHROPATHY

Abstract Background and Aims Our previous study demonstrated lipid accumulation contributes to tubulointerstitial injury in diabetic nephropathy. However, the exact mechanism of which accelerate tubulointerstitium has not been completely elucidated. Increasing studies suggest that chronic hypoxia plays an important pathophysiologic role This aimed investigate effect inducible factor-1α (HIF-1α) activation induced by on kidney explore its potential mechanism. Method Human proximal tubular cell line HK-2 was incubated with or without cobalt chloride (CoCl2, 100 μM) stimulates hypoxic condition presence absence glucose (30 mM) for 24 h. Specific siRNA transfected cells knock down HIF-1α expression. Type 1 rats model were STZ injection, Lificiguat (YC-1) used as inhibitor intraperitoneal injection. Immunofluorescence staining Western blot determine cellular localization expression HIF-1α. Periodic Acid-Schiff (PAS) observe basic structure pathological changes kidney. The carnitine palmitoyl transferase 1A (CPT1A), tissue growth factor-β1 (TGF-β1), connective factor (CTGF) measured immunohistochemical blot. Lipid detected oil red O triglyceride quantification assay. Results In vitro study, CoCl2 effectively increased translocation from cytoplasm nucleus. Meanwhile, significantly cells. Moreover, treatment TGF- β CTGF (30mM) made no significant difference CoCl2. reduced deposition vivo showed YC-1 decreased renal tubules rats, accompanied less compared diabetes mellitus (DM) group. PAS desquamation necrosis epithelial group alleviated DM did affect ratio weight body weight, whereas levels blood glucose, urine albumin creatinine NAG rats. expressions fibrosis Furthermore, protein CPT1A, key enzyme fatty acid oxidation, controls, regained treatment. Conclusion findings contributed interstitial nephropathy inducing accumulation. might contribute nephrotoxicity downregulating oxidation.