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
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.
