A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease

被引:13
|
作者
Nakatsuka, Atsuko [1 ,2 ]
Yamaguchi, Satoshi [1 ]
Eguchi, Jun [1 ]
Kakuta, Shigeru [3 ]
Iwakura, Yoichiro [4 ]
Sugiyama, Hitoshi [5 ]
Wada, Jun [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Nephrol Rheumatol Endocrinol & Metab, Kita Ku, Okayama 7008558, Japan
[2] Okayama Univ Hosp, Div Kidney Diabet & Endocrine Dis, Kita Ku, Okayama 7008558, Japan
[3] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Tokyo 1138657, Japan
[4] Tokyo Univ Sci, Res Inst Biomed Sci, Chiba 2780022, Japan
[5] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Human Resource Dev Dialysis Therapy Kidney D, Kita Ku, Okayama 7008558, Japan
关键词
D O I
10.1038/s42003-021-01902-y
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD.
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页数:16
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