关键词: 糖尿病肾病, 肾小管上皮细胞, 肾损伤分子1, 自噬

Abstract:

【Abstract】 Objective To research the effects of Kidney Injury Molecule 1（KIM-1）on high glucose induced the autophagy in human tubular epithelial cells (HK2) and to explore the possible mechanisms of KIM-1 involved in the progress of diabetic nephropathy (DN). Methodology: HK2 were cultured in vitro and divided into different groups. They were (1) Normal control Group (D-glucose 5.6 mmol／L); (2) Hypertonic group (D-glucose 5.6 mmol／L+D-mannitol 24.4 mmol／L); (3) High glucose group (D-glucose 30 mmol／L); (4) KIM-1 siRNA group; and (5) Control siRNA group．The corresponding indexes were measured at 8th, 16th and 24th hours. Western blotting was used to detect the protein expression of KIM-1 and autophagy protein 3 (microtubule-associated protein 1 light chain 3II（LC3II）. Real Time-PCR was used to detect mRNA expression of KIM-1 and LC3II. The autophagosomes formed in human tubular epithelial cells were observed by transmission electron microscope (TEM) .Results: Compared with the control group, the protein and mRNA expression of KIM-1 and LC3II in the high glucose group were increased (P<0.05), and the number of autophagosomes were also added in a time-dependent manner (P<0.05). Compared with the high glucose group, the protein and mRNA expressions of KIM-1 and LC3II were decreased (P<0.05), and the number of autophagosomes were reduced in KIM-1 siRNA group (P<0.05). Conclusions Down-regulating the expression of KIM-1 can inhibit the expression of LC3II and the formation of autophagosomes, which suggests that KIM-1 may be involved in the progress of DN by regulating the autophagy in human tubular epithelial cells.

Key words: Diabetic nephropathy, renal tubular epithelial cell, Kidney injury factor-1, Autophagy