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

Published on Mar 19, 2021
· DOI :10.1038/S42003-021-01902-Y
Atsuko Nakatsuka17
Estimated H-index: 17
(Okayama University),
Satoshi Yamaguchi4
Estimated H-index: 4
(Okayama University)
+ 4 AuthorsJun Wada64
Estimated H-index: 64
(Okayama University)
Sources
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. Nakatsuka et al. discover that the adipokine vaspin contributes to maintaining proximal tubular cell (PTC) homeostasis by ameliorating organelle stress. They find that upon internalization, vaspin interacts with the heat shock protein HSPA1L and that the proteins cooperate to prevent metabolic stress-induced cellular injuries in PTCs.
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References47
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Background: Heat shock protein family A member 1 like (Hspa1l) is a member of the 70kD heat shock protein (Hsp70) family. HSPA1L is an ancient, evolutionarily conserved gene with a highly conserved domain structure. The gene is highly abundant and constitutively expressed in the mice testes. However, the role of Hspa1l in the testes has still not been elucidated. Methods: Hspa1l-mutant mice were generated using the CRISPR/Cas9 system. Histological and immunofluorescence staining were used to ana...
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#1Xinnong Chen (Tianjin University of Traditional Chinese Medicine)H-Index: 2
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#1Hilla Chen (HUJI: Hebrew University of Jerusalem)H-Index: 3
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#1Susmita Kaushik (Albert Einstein College of Medicine)H-Index: 48
#2Ana Maria Cuervo (Albert Einstein College of Medicine)H-Index: 123
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#4Robert J. Unwin (UCL: University College London)H-Index: 64
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#1Jaakko Sarparanta (Albert Einstein College of Medicine)H-Index: 19
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#1Richard E. Gilbert (St. Michael's Hospital)H-Index: 84
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#1San Min Leow (NUS: National University of Singapore)H-Index: 1
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// San Min Leow 1,2 , Shu Xian Serene Chua 1 , Gireedhar Venkatachalam 1,2 , Liang Shen 3 , Le Luo 1 and Marie-Veronique Clement 1,2 1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 2 National University of Singapore Graduate School for Integrative Sciences and Engineering, Singapore, Singapore 3 Biostatistic Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Correspondence to: Marie-V...
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