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

Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Eguchi, Shigeru Kakuta, Yoichiro Iwakura, Hitoshi Sugiyama, Jun Wada

Research output: Contribution to journalArticlepeer-review

Abstract

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 78 kDa 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.

Original languageEnglish
Article number373
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'A Vaspin–HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease'. Together they form a unique fingerprint.

Cite this