Dataset Information

Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids.

ABSTRACT:

Background

Renal proximal tubulopathy plays a crucial role in kidney disease, but its molecular mechanism is incompletely understood. Because proximal tubular cells consume a lot of energy during reabsorption, the relationship between fatty acids (FAs) and proximal tubulopathy has been attracting attention. The purpose of this study is to investigate the association between change in renal FA composition and tubulopathy.

Methods

Mice with cisplatin-induced nephrotoxicity were used as a model of AKI and 5/6-nephrectomized mice were used as a model of CKD. Renal FA composition in mice was measured by GC-MS. Human tubular epithelial cells (HK-2 cells) were used for in vitro studies.

Results

In kidneys of AKI mice, increased stearic acid (C18:0) and decreased palmitic acid (C16:0) were observed, accompanied by increased expression of the long-chain FA elongase Elovl6. Similar results were also obtained in CKD mice. We show that C18:0 has higher tubular toxicity than C16:0 via induction of ER stress. Using adenovirus-expressing Elovl6 or siRNA for Elovl6 in HK-2 cells, we demonstrated that increased Elovl6 expression contributes to tubulopathy via increasing C18:0. Elovl6 knockout suppressed the increased serum creatinine levels, renal ER stress, and inflammation that would usually result after 5/6 nephrectomy. Advanced oxidation protein products (AOPPs), specifically an oxidized albumin, was found to induce Elovl6 via the mTORC1/SREBP1 pathway.

Conclusions

AOPPs may contribute to renal tubulopathy via perturbation of renal FAs through induction of Elovl6. The perturbation of renal FAs induced by the AOPPs-Elovl6 system could be a potential target for the treatment of tubulopathy.

SUBMITTER: Imafuku T

PROVIDER: S-EPMC8815742 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Advanced Oxidation Protein Products Contribute to Renal Tubulopathy <i>via</i> Perturbation of Renal Fatty Acids.

Imafuku Tadashi T Watanabe Hiroshi H Satoh Takao T Matsuzaka Takashi T Inazumi Tomoaki T Kato Hiromasa H Tanaka Shoma S Nakamura Yuka Y Nakano Takehiro T Tokumaru Kai K Maeda Hitoshi H Mukunoki Ayumi A Takeo Toru T Nakagata Naomi N Tanaka Motoko M Matsushita Kazutaka K Tsuchiya Soken S Sugimoto Yukihiko Y Shimano Hitoshi H Fukagawa Masafumi M Maruyama Toru T

Kidney360 20200603 8

<h4>Background</h4>Renal proximal tubulopathy plays a crucial role in kidney disease, but its molecular mechanism is incompletely understood. Because proximal tubular cells consume a lot of energy during reabsorption, the relationship between fatty acids (FAs) and proximal tubulopathy has been attracting attention. The purpose of this study is to investigate the association between change in renal FA composition and tubulopathy.<h4>Methods</h4>Mice with cisplatin-induced nephrotoxicity were used ...[more]

PMID: 35372949

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