Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury

作者全名："Cai, Meng-yao; Jiang, Xu-shun; Wei, Yun-xin; Wen, Rui-zhi; Du, Xiao-gang"

作者地址："[Cai, Meng-yao; Jiang, Xu-shun; Wei, Yun-xin; Wen, Rui-zhi; Du, Xiao-gang] Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Youyi Rd 1, Chongqing 400042, Peoples R China; [Du, Xiao-gang] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Youyi Rd 1, Chongqing 400042, Peoples R China"

通信作者："Du, XG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Youyi Rd 1, Chongqing 400042, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001167366700001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：696

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Palmitic acid; TFEB; autophagy; Lysosome; Renal tubular epithelial cells

摘要："Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagylysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury."

基金机构：Natural Science Foundation Project of Chongqing [cstc2019jcyj-msxmX0504]; National Natural Science Foundation of China [82200799]

基金资助正文：This work was supported by the Natural Science Foundation Project of Chongqing (No. cstc2019jcyj-msxmX0504) and National Natural Science Foundation of China (No. 82200799) .