Abstract: Ｏｂｊｅｃｔｉｖｅ：To investigate effect and mechanism of kidney injury molecule-1 (KIM-1) mediated immunoglobulin free light chains (FLCs) endocytosis on renal tubular injury and fibrosis in renal tubular epithelial cells.
Ｍｅｔｈｏｄｏｌｏｇｙ：(1) urine samples from 4 patients with multiple myeloma were selected and FLCs were purified by ion exchange chromatography;(2) the model of HK-2 cell injury was induced by FLCs extracted by the above method in vitro. FLCs stimulation was continued and KIM-1 inhibitor TW-37 was used to treat it.After continous intraperitoneal injection of FLCs for 14 days into mice in vivo, the animal model of renal tubular injury induced by FLCs was established and interfered with TW-37. The levels of KIM-1, TGF-β etc in HK-2 cells and renal tissue were detected by Western Blot. The Ratio of urinary albumin protein to creatinine and content of KIM-1 in urine were detected by ELISA method, and the degree of renal interstitial fibrosis was detected by Sirius red staining.
Ｒｅｓｕｌｔｓ：(1) in vitro, FLCs stimulated HK-2 cells to increase expression of KIM-1, which was co-localization of KIM-1 and FLCs in HK-2 cells. TW-37 treatment can reduce FLCs endocytosis in HK-2 cells, reduce perinuclear aggregation of lysosomes in renal tubular cells stimulated by FLCs, and reduce expression of oxidative stress and fibrosis indexes. The results of animal model showed that TW-37 can alleviate renal tubular injury induced by FLCs, such as decrease of KIM-1 content in urine and expression of KIM-1 in renal tissue, the decrease of oxidative stress, fibrosis index and collagen deposition in renal tissue.
Ｃｏｎｃｌｕｓｉｏｎ：KIM-1 can mediate endocytosis of FLCs by renal proximal tubular cells, and inhibition of KIM-1 may alleviate renal injury caused by FLCs.

Key words: renal tubular epithelial cell, immunoglobulin free light chain, kidney injury molecule-1, endocytosis, TW-37