Mar 19, 2021
A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease.
Communications biology
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- Volume
- 4
- Number
- 1
- First page
- 373
- Last page
- 373
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1038/s42003-021-01902-y
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.
- Link information
- ID information
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- DOI : 10.1038/s42003-021-01902-y
- Pubmed ID : 33742129
- Pubmed Central ID : PMC7979793