Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis—Pharmacomodulation of Rosuvastatin

Pei-Hsun Sung; Ben-Chung Cheng; Tsuen-Wei Hsu; John Y Chiang; Hsin-Ju Chiang; Yi-Ling Chen; Chih-Chao Yang; Hon-Kan Yip

doi:10.3390/antiox11122465

Antioxidants (Dec 2022)

Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis—Pharmacomodulation of Rosuvastatin

Pei-Hsun Sung,
Ben-Chung Cheng,
Tsuen-Wei Hsu,
John Y Chiang,
Hsin-Ju Chiang,
Yi-Ling Chen,
Chih-Chao Yang,
Hon-Kan Yip

Affiliations

Pei-Hsun Sung: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
Ben-Chung Cheng: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
Tsuen-Wei Hsu: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
John Y Chiang: Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung 804201, Taiwan
Hsin-Ju Chiang: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
Yi-Ling Chen: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
Chih-Chao Yang: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
Hon-Kan Yip: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan

DOI: https://doi.org/10.3390/antiox11122465
Journal volume & issue: Vol. 11, no. 12
p. 2465

Abstract

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This study tested the hypothesis that intrarenal arterial transfusion of oxidized low-density lipoprotein (ox-LDL) jeopardized the residual renal function and kidney architecture in rat chronic kidney disease ((CKD), i.e., induced by 5/6 nephrectomy) that was reversed by rosuvastatin. Cell culture was categorized into A1 (NRK-52E cells), A2 (NRK-52E + TGF-β), A3 (NRK-52E + TGF-β + ox-LDL) and A4 (NRK-52E + TGF-β + ox-LD). The result of in vitro study showed that cell viability (at 24, 48 and 72 h), NRK-52E ox-LDL-uptake, protein expressions of epithelial–mesenchymal–transition (EMT) markers (i.e., p-Smad2/snail/α-SMA/FSP1) and cell migratory and wound healing capacities were significantly progressively increased from A1 to A4 (all p p p < 0.0001). In conclusion, ox-LDL damaged the residual renal function and kidney ultrastructure in CKD mainly through augmenting oxidative stress, EMT and fibrosis that was remarkably reversed by rosuvastatin.

Published in Antioxidants

ISSN: 2076-3921 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antioxidants

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