Impact of Ring Finger Protein 20 and Its Downstream Regulation on Renal Tubular Injury in a Unilateral Nephrectomy Mouse Model Fed a High-Fat Diet

Author:

Kim You-Jin12ORCID,Oh Se-Hyun12,Lim Jeong-Hoon123ORCID,Cho Jang-Hee12ORCID,Jung Hee-Yeon1,Kim Chan-Duck1ORCID,Park Sun-Hee1ORCID,Kwon Tae-Hwan4ORCID,Kim Yong-Lim12ORCID

Affiliation:

1. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea

2. Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea

3. Division of Nephrology, Department of Intermanl Medicine, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea

4. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea

Abstract

Abnormal lipid metabolism increases the relative risk of kidney disease in patients with a single kidney. Using transcriptome analysis, we investigated whether a high-fat diet leads to abnormalities in lipid metabolism and induces kidney cell-specific damage in unilateral nephrectomy mice. Mice with unilateral nephrectomy fed a high-fat diet for 12 weeks exhibited progressive renal dysfunction in proximal tubules, including lipid accumulation, vacuolization, and cell damage. Ring finger protein 20 (RNF20) is a ligase of nuclear receptor corepressor of peroxisome proliferator-activated receptors (PPARs). The transcriptome analysis revealed the involvement of RNF20-related transcriptome changes in PPAR signaling, lipid metabolism, and water transmembrane transporter under a high-fat diet and unilateral nephrectomy. In vitro treatment of proximal tubular cells with palmitic acid induced lipotoxicity by altering RNF20, PPARα, and ATP-binding cassette subfamily A member 1 (ABCA1) expression. PPARγ and aquaporin 2 (AQP2) expression decreased in collecting duct cells, regulating genetic changes in the water reabsorption process. In conclusion, a high-fat diet induces lipid accumulation under unilateral nephrectomy via altering RNF20-mediated regulation and causing functional damage to cells as a result of abnormal lipid metabolism, thereby leading to structural and functional kidney deterioration.

Funder

National Research Foundation of Korea

Korea Health Industry Development Institute

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

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