Proteomics and Transcriptomics Profiling Reveals Distinct Aspects of Kidney Stone Related Genes in Calculi Rats

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2023 Mar 18

PMID 36932340

Authors

Wang Zhu

Deng Qiong

Gu Yanli

Li Min

Zhang Ying

Hu Qiyi

Zhang Shenping

Wang Xisheng

Liang Hui

Affiliations

Soon will be listed here.

Abstract

Backgrounds: Kidney stone also known as urolithiasis or nephrolithiasis, is one of the oldest diseases known to medicine, however, the gene expression changes and related kidney injury remains unclear.

Methods: A calculi rat model was developed via ethylene glycol- and ammonium chloride-induction. Integrated proteomic and transcriptomic analysis was performed to characterize the distinct gene expression profiles in the kidney of calculi rat. Differential expressed genes (DEGs) were sub-clustered into distinct groups according to the consistency of transcriptome and proteome. Gene Ontology and KEGG pathway enrichment was performed to analyze the functions of each sub-group of DEGs. Immunohistochemistry was performed to validated the expression of identified proteins.

Results: Five thousand eight hundred ninety-seven genes were quantified at both transcriptome and proteome levels, and six distinct gene clusters were identified, of which 14 genes were consistently dysregulated. Functional enrichment analysis showed that the calculi rat kidney was increased expression of injured & apoptotic markers and immune-molecules, and decreased expression of solute carriers & transporters and many metabolic related factors.

Conclusions: The present proteotranscriptomic study provided a data resource and new insights for better understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of new strategies for the recurrence prevention and treatment in patients with kidney stone disease.

Citing Articles

Integrated proteomics reveals enrichment of oxidative stress and inflammatory proteins in the urine and stone matrix of calcium oxalate stone formers.

Suttapitugsakul S, Sassanarakkit S, Peerapen P, Thongboonkerd V Urolithiasis. 2025; 53(1):25.

PMID: 39912926 DOI: 10.1007/s00240-025-01697-1.

Revealing the molecular landscape of calcium oxalate renal calculi utilizing a tree shrew model: a transcriptomic analysis of the kidney.

Wang G, Huang Z, Wu Y, Xu R, Li J Urolithiasis. 2024; 52(1):161.

PMID: 39546021 DOI: 10.1007/s00240-024-01661-5.

The Altered Proteomic Landscape in Renal Tubular Epithelial Cells under High Oxalate Stimulation.

Hong S, Qin B Biology (Basel). 2024; 13(10).

PMID: 39452123 PMC: 11505525. DOI: 10.3390/biology13100814.

Transcriptional activation of PINK1 by MyoD1 mediates mitochondrial homeostasis to induce renal calcification in pediatric nephrolithiasis.

Zhang K, Fang X, Zhang Y, Zhang Y, Chao M Cell Death Discov. 2024; 10(1):397.

PMID: 39242558 PMC: 11379875. DOI: 10.1038/s41420-024-02117-w.

References

Cao Y, Gao X, Yang Y, Ye Z, Wang E, Dong Z . Changing expression profiles of long non-coding RNAs, mRNAs and circular RNAs in ethylene glycol-induced kidney calculi rats. BMC Genomics. 2018; 19(1):660. PMC: 6131827. DOI: 10.1186/s12864-018-5052-8. View

Lin S, Lin C, Chang Y, Hsu W, Lin C, Wang I . Association Between Kidney Stones and Risk of Stroke: A Nationwide Population-Based Cohort Study. Medicine (Baltimore). 2016; 95(8):e2847. PMC: 4779012. DOI: 10.1097/MD.0000000000002847. View

Wang Z, Li Y, Wu D, Yu S, Wang Y, Chan F . Nuclear receptor HNF4α performs a tumor suppressor function in prostate cancer via its induction of p21-driven cellular senescence. Oncogene. 2019; 39(7):1572-1589. PMC: 7018660. DOI: 10.1038/s41388-019-1080-3. View

Wawryk-Gawda E, Chlapek K, Zarobkiewicz M, Lis-Sochocka M, Chylinska-Wrzos P, Boguszewska-Czubara A . CB2R agonist prevents nicotine induced lung fibrosis. Exp Lung Res. 2019; 44(7):344-351. DOI: 10.1080/01902148.2018.1543368. View

Noris M, Remuzzi G . Overview of complement activation and regulation. Semin Nephrol. 2013; 33(6):479-92. PMC: 3820029. DOI: 10.1016/j.semnephrol.2013.08.001. View

Bishop K, Momah T, Ricks J . Nephrolithiasis. Prim Care. 2020; 47(4):661-671. DOI: 10.1016/j.pop.2020.08.005. View

Khan S, Pearle M, Robertson W, Gambaro G, Canales B, Doizi S . Kidney stones. Nat Rev Dis Primers. 2016; 2:16008. PMC: 5685519. DOI: 10.1038/nrdp.2016.8. View

Joshi S, Wang W, Peck A, Khan S . Activation of the NLRP3 inflammasome in association with calcium oxalate crystal induced reactive oxygen species in kidneys. J Urol. 2014; 193(5):1684-91. PMC: 4406847. DOI: 10.1016/j.juro.2014.11.093. View

Albert A, Paul E, Rajakumar S, Saso L . Oxidative stress and endoplasmic stress in calcium oxalate stone disease: the chicken or the egg?. Free Radic Res. 2020; 54(4):244-253. DOI: 10.1080/10715762.2020.1751835. View

10.

Zhang P, Azad P, Engelhart D, Haddad G, Nigam S . SLC22 Transporters in the Fly Renal System Regulate Response to Oxidative Stress In Vivo. Int J Mol Sci. 2021; 22(24). PMC: 8706193. DOI: 10.3390/ijms222413407. View

11.

Zinad H, Sae-Lee C, Ariza-Mateos M, Adamson G, Khazeem M, Knox A . Interdependent Transcription of a Natural Sense/Antisense Transcripts Pair (). Noncoding RNA. 2022; 8(1). PMC: 8877773. DOI: 10.3390/ncrna8010019. View

12.

Koh A, Paes Batista da Silva A, Bansal A, Bansal M, Sun C, Lee H . Role of osteopontin in neutrophil function. Immunology. 2007; 122(4):466-75. PMC: 2266047. DOI: 10.1111/j.1365-2567.2007.02682.x. View

13.

Wagner C, Hernando N, Forster I, Biber J . The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch. 2013; 466(1):139-53. DOI: 10.1007/s00424-013-1418-6. View

14.

Sun Y, Kang J, Guan X, Xu H, Wang X, Deng Y . Regulation of endoplasmic reticulum stress on the damage and apoptosis of renal tubular epithelial cells induced by calcium oxalate crystals. Urolithiasis. 2021; 49(4):291-299. DOI: 10.1007/s00240-021-01261-7. View

15.

Khan S . Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. Transl Androl Urol. 2014; 3(3):256-276. PMC: 4220551. DOI: 10.3978/j.issn.2223-4683.2014.06.04. View

16.

Zhu B, Suzuki K, Goldberg H, Rittling S, Denhardt D, McCulloch C . Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors: evidence of a role for an intracellular form of osteopontin. J Cell Physiol. 2003; 198(1):155-67. DOI: 10.1002/jcp.10394. View

17.

Yang L, Brooks C, Xiao S, Sabbisetti V, Yeung M, Hsiao L . KIM-1-mediated phagocytosis reduces acute injury to the kidney. J Clin Invest. 2015; 125(4):1620-36. PMC: 4396492. DOI: 10.1172/JCI75417. View

18.

Ashkar S, Weber G, Panoutsakopoulou V, Sanchirico M, Jansson M, Zawaideh S . Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000; 287(5454):860-4. DOI: 10.1126/science.287.5454.860. View

19.

Li C, Chien T, Wu W, Huang C, Chou Y . Uric acid stones increase the risk of chronic kidney disease. Urolithiasis. 2018; 46(6):543-547. DOI: 10.1007/s00240-018-1050-1. View

20.

Hesse A, Frick M, Orzekowsky H, Failing K, Neiger R . Canine calcium oxalate urolithiasis: Frequency of Whewellite and Weddellite stones from 1979 to 2015. Can Vet J. 2018; 59(12):1305-1310. PMC: 6237259. View