Deciphering the Expression of Klotho, Superoxide Dismutase 1, Catalase, p53, and Cyclophilin Genes in Pathogenesis of Chronic Kidney Disease
Keywords:
CKD, AKI, Kidney, Disease, Pathogenesis.Abstract
OBJECTIVE: To analyze the expression of genes involved in OS scavenging defense activation and to understand their contribution to CKD pathogenesis.
METHODOLOGY: A case-control study was conducted among 150 participants in Ibn-e-Sina Hospital, Multan, from January to August 2023. The relative expression of antioxidants, including Klotho (KL), Catalase (CAT), Cyclophilin A (CyPA), tumor protein p53 (p53), and Superoxide dismutase 1 (SOD1), was quantified using gene-specific primers and real-time qPCR. Data were analyzed by one-way analysis of variance (ANOVA) via GraphPad Prism. The correlation among the KL, CAT, and SOD1 genes was evaluated via matrix scatter plots.
RESULTS: The results show that the relative expression of KL and CAT genes was significantly downregulated in acute kidney injury (AKI) and CKD patients, whereas SOD1 was upregulated in AKI and downregulated in CKD patients compared with controls. The levels of p53 were upregulated by >3-fold in CKD and AKI patients. CyPA was upregulated by >1.5-fold in patients with CKD and AKI. Across CKD stages, the levels of KL and CAT were downregulated, while SOD1 was unaffected. The levels of p53 were >9-fold, 6-fold, and >3-fold upregulated in CKD stages 5 to 3, respectively. CyPA was >1.8-fold upregulated in stages 5 and 4 versus control. The KL gene was positively correlated with the CAT gene.
CONCLUSION: Differential expression levels of KL, CAT, SOD1, p53, and CyPA genes suggest their potential role in mediating OS scavenging, regulation, pathogenesis, and progression of kidney disease.
References
1. Liu P, Quinn RR, Lam NN, Elliott MJ, Xu Y, James MT et al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021; 181(10): 1359-66.
2. Quadri MM, Fatima S-S, Che R-C, Zhang A-H. Mitochondria and renal fibrosis. Renal Fibrosis: Mechanisms and Therapies. Adv Exp Med Biol. 2019:501-24.
3. He L, Wei Q, Liu J, Yi M, Liu Y, Liu H et al. AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms. Kidney Int. 2017; 92(5): 1071-83.
4. Thérond P, Bonnefont-Rousselot D, Davit-Spraul A, Conti M, Legrand A. Biomarkers of oxidative stress: an analytical approach. Curr Opin Clin Nutr Metab Care, 2000; 3(5): 373-84.
5. Donate-Correa J, Martín-Carro B, Cannata-Andía JB, Mora-Fernández C, Navarro-González JF. Klotho, oxidative stress, and mitochondrial damage in kidney disease. Antioxidants, 2023; 12(2): 239.
6. Tirichen H, Yaigoub H, Xu W, Wu C, Li R, Li Y. Mitochondrial reactive oxygen species and their contribution in chronic kidney disease progression through oxidative stress. Front Physiol. 2021; 12: 627837.
7. Hong YA, Park CW. Catalytic Antioxidants in the Kidney. Antioxidants, 2021; 10(1).
8. Carmo de Carvalho e Martins, da Silva Santos Oliveira AS, da Silva LAA, Primo MGS, de Carvalho Lira VB. Biological indicators of oxidative stress [malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase] and their application in nutrition. Biomarkers in nutrition: Springer; 2022; 833-56.
9. Sakan H, Nakatani K, Asai O, Imura A, Tanaka T, Yoshimoto S et al. Reduced renal ?-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism. PloS One, 2014; 9(1): e86301.
10. Capuozzo M, Santorsola M, Bocchetti M, Perri F, Cascella M, Granata V, et al. p53: from fundamental biology to clinical applications in cancer. Biol. 2022; 11(9): 1325.
11. Chinnam M, Xu C, Lama R, Zhang X, Cedeno CD, Wang Y et al. MDM2 E3 ligase activity is essential for p53 regulation and cell cycle integrity. PloS Genet. 2022; 18(5): e1010171.
12. Ye Z, Xia Y, Li L, Li B, Chen L, Yu W, et al. p53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis. Biomed Pharmacother. 2023; 164: 114925.
13. Hadpech S, Thongboonkerd V. Current update on theranostic roles of cyclophilin A in kidney diseases. Theranostics, 2022; 12(9): 4067.
14. Yang W-C, Hsieh H-M, Chen J-P, Liu L-C, Chen C-H. Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3–5: a randomized controlled trial. BMC Nephrol. 2023; 24(1): 372.
15. Hassan MH, Saleem TH, Abdallah AAM, Abdelhady M, Salama DA-E, Elsaied AA et al. Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements. Egypt J Intern Med. 2025; 37(1): 5.
16. Shimamura Y, Hamada K, Inoue K, Ogata K, Ishihara M, Kagawa T et al. Serum levels of soluble secreted ?-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol. 2012; 16(5): 722-729.
17. Devaraj S, Syed B, Chien A, Jialal I. Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease. Am J Clin Pathol. 2012; 137(3): 479-485.
18. Sulaiman SH, Demir H, Soyoral YU, Demir C. Determination of oxidative stress levels and some antioxidant activities in acute and chronic renal failure patients. J Clin Chem Lab Med. 2021; 7(1): 12-29.
19. Pathare G, Raju S, Mashru M, Shah V, Shalia K. ?-Klotho and catalase expression in essential hypertension. Integr Mol Med. 2020; 7: 1-6.
20. Scholze A, Krueger K, Diedrich M, Räth C, Torges A, Jankowski V et al. Superoxide dismutase type 1 in monocytes of chronic kidney disease patients. Amino Acids, 2011; 41(2): 427-438.
21. Ye Z, Xia Y, Li L, Li B, Chen L, Yu W et al. p53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis. Biomed. Pharmacother. 2023; 164: 114925.
22. Zhen X, Sun Y, Lin H, Huang Y, Liu T, Li Y et al. Elucidating the role of nicotinamide N-methyltransferase-p53 axis in the progression of chronic kidney disease. PeerJ. 2023; 11: e16301.
23. Ming WH, Wen L, Hu WJ, Qiao RF, Zhou Y, Su BW et al. The crosstalk of Wnt/?-catenin signaling and p53 in acute kidney injury and chronic kidney disease. Kidney Res Clin Pract. 2024; 43(6): 724-38.
24. Luo C, Zhou S, Zhou Z, Liu Y, Yang L, Liu J et al. Wnt9a promotes renal fibrosis by accelerating cellular senescence in tubular epithelial cells. J Am Soc Nephrol. 2018; 29(4): 1238-56.
25. Lee C-C, Chang C-H, Cheng Y-L, Kuo G, Chen S-W, Li Y-J et al. Diagnostic performance of cyclophilin a in cardiac surgery-associated acute kidney injury. J Clin Med. 2019; 9(1): 108.
26. Chatchawal P, Tippayawat P, Somdee T, Ngernpimai S, Wongwattanakul M, Sae-ung N, et al. Urinary cyclophilin A as an early marker of chronic kidney disease with underlying type 2 diabetes. Sci Rep. 2024; 14(1): 23207.
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