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

• Nakatsuka, Atsuko

• Yamaguchi, Satoshi

• Eguchi, Jun

• Kakuta, Shigeru

• Iwakura, Yoichiro

• Sugiyama, Hitoshi

• Wada, Jun

抄録

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.

収録刊行物

• Communications Biology

  Communications Biology 4 (1), 373-, 2021-03-19

  Nature

キーワード

• General Agricultural and Biological Sciences
• General Biochemistry, Genetics and Molecular Biology
• Medicine (miscellaneous)

詳細情報

• CRID: 1050850545623222400
• NII論文ID: 120007004153
• ISSN: 23993642
• DOI: 10.1038/s42003-021-01902-y
• Web Site: https://ousar.lib.okayama-u.ac.jp/61600
• Web Site: https://www.nature.com/articles/s42003-021-01902-y.pdf
• Web Site: https://www.nature.com/articles/s42003-021-01902-y
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN