AIM: To investigate the effects of pathological products, urinary proteins and advanced glycosylation end products (AGE) produced in the progression of chronic kidney disease (CKD), on the structure and function of lysosomes in renal tubular epithelial cells (TECs), and try to find a novel approach for preventing or delaying CKD. METHODS: The renal specimens of the untreated patients with minimal change nephrotic syndrome (MCNS), diabetic nephropathy (DN) or normal kidney were collected. The expression of lysosomal-associated membrane protein 1 (LAMP1) and cathepsin B (CB) was studied in TECs by indirect immunofluorescent staining. Human renal tubular epithelial cell line HK-2 was incubated with 8 g/L urinary proteins or 100 mg/L AGE. The expression of LAMP1 and CB was investigated by indirect immunofluorescence and the activity of CB and cathepsin L (CL) was measured by biochemical and enzymatic assays.The degradation of DQ-ovalbumin was also determined. RESULTS: The lysosomal membrane permeabilization occurred in the TECs of MCNS and DN patients. After treatment with urinary proteins or AGE-BSA, the lysosomal membrane permeabilization of the HK-2 cells was increased. The activity of CB and CL and degradation of DQ-ovalbumin were decreased as compared with normal control group. CONCLUSION: The digestive function of lysosome was decreased and lysosomal membrane permeabilization occurred in the TECs exposed to urinary proteins and AGE, which might be a key factor to induce the tubulointerstitial fibrosis.
邓健锟, 王淑君, 吴洪銮, 罗勉娜, 许碧华, 梁东, 潘庆军, 刘华锋, 刘伟敬. 尿蛋白及晚期糖基化终产物对肾小管上皮细胞溶酶体的影响[J]. 中国病理生理杂志, 2015, 31(3): 505-510.
DENG Jian-kun, WANG Shu-jun, WU Hong-luan, LUO Mian-na, XU Bi-hua, LIANG Dong, PAN Qing-jun, LIU Hua-feng, LIU Wei-jing. Effect of urinary proteins and advanced glycosylation end products on lysosomes in renal tubular epithelial cells. Chin J Pathophysiol, 2015, 31(3): 505-510.
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