ID | 61600 |
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Nakatsuka, Atsuko
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Yamaguchi, Satoshi
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Eguchi, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kakuta, Shigeru
Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, the University of Tokyo
Iwakura, Yoichiro
Research Institute for Biomedical Sciences, Tokyo University of Science
Sugiyama, Hitoshi
Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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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 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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Published Date | 2021-03-19
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Publication Title |
Communications Biology
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Volume | volume4
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Issue | issue1
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Publisher | Nature
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Start Page | 373
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ISSN | 2399-3642
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2021
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1038/s42003-021-01902-y
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License | http://creativecommons.org/licenses/by/4.0/
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