Top

BMC Nephrology

Published in:

Open Access 01-12-2016 | Research article

Identification of potential candidate genes for hypertensive nephropathy based on gene expression profile

Authors: Zhi Chen, Hao Wu, Guohua Wang, Ye Feng

Published in: BMC Nephrology | Issue 1/2016

Abstract

Background

This study was aimed to explore the molecular mechanisms of hypertensive nephropathy (HTN).

Methods

Gene expression profile of GSE37460, which based on 27 healthy living donor samples (HTN group) and 15 hypertensive nephropathy samples (control group), were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between two groups were identified. STRING database was used to reveal protein-protein interaction (PPI) network of DEGs, followed by the functional enrichment analysis of the PPI network. Additionally, miRNA-DEG regulatory network was constructed to reveal the validated miRNAs targeting the DEGs.

Results

In total, 51 up-regulated genes and 140 down-regulated genes were obtained. In the PPI network, cytochrome P450 3A4 (CYP3A4) and angiotensin II receptor type 1 (AGTR1) had a higher degree, and CYP3A4 interacted with CYP4A11. The DEGs in the network were significantly enriched in drug metabolism, focal adhesion and arachidonic acid metabolism. Furthermore, in the miRNA-DEG regulatory network, hsa-miR-335-5p and hsa-miR-26b-5p were the two most outstanding miRNAs. AGTR1, CYP3A4 and CYP4A11 were predicted to be regulated by hsa-miR-26b-5p.

Conclusion

The DEGs, such as AGTR1, CYP3A4 and CYP4A11 may play critical roles in the development of HTN likely via the regulation by hsa-miR-26b-5p and taking part in some pathways.

Toto RB. Nephrology Forum - Hypertensive nephrosclerosis in African Americans. Kidney Int. 2003;64(10):2331–41.PubMedCrossRef

Rutkowski B, Tylicki L, Manitius J, Lysiak-Szydlowska W. Hypertensive nephropathy - an increasing clinical problem. Miner Electrolyte Metab. 1999;25(1-2):65–8.PubMedCrossRef

Uchida S, Takahashi M, Sugawara M, Saito T, Nakai K, Fujita M, et al. Effects of the N/L-type calcium channel blocker cilnidipine on nephropathy and uric acid metabolism in hypertensive patients with chronic kidney disease (J-CIRCLE study). J Clin Hypertens. 2014;16(10):746–53.CrossRef

Baltatu OC, Zaugg CE, Schumacher C, Louie P, Campos LA, Bader M. Avosentan is protective in hypertensive nephropathy at doses not causing fluid retention. Pharmacol Res. 2014;80:9–13.PubMedCrossRef

Wang XC, Liu CH, Chen YJ, Wu Y, Yang LS, Liu HM, et al. Clinical and pathological analysis of the kidney in patients with hypertensive nephropathy. Exp Ther Med. 2013;6(5):1243–46.PubMedPubMedCentral

Hart PD, Bakris GL. Hypertensive nephropathy: prevention and treatment recommendations. Expert Opin Pharmacother. 2010;11(16):2675–86.PubMedCrossRef

Dmitrieva RI, Hinojos CA, Boerwinkle E, Braun MC, Fornage M, Doris PA. Hepatocyte nuclear factor 1 and hypertensive nephropathy. Hypertension. 2008;51(6):1583–9.PubMedPubMedCentralCrossRef

Guerrot D, Dussaule J-C, Mael-Ainin M, Xu-Dubois Y-C, Rondeau E, Chatziantoniou C, et al. Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy. PLoS One. 2012;7(3):e31974.PubMedPubMedCentralCrossRef

Liu G-X, Li Y-Q, Huang XR, Wei LH, Zhang Y, Feng M, et al. Smad7 inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension. Clin Sci. 2014;127(3):195–208.PubMedCrossRef

10.

Wang G, Kwan BC-H, Lai FM-M, Choi PC-L, Chow K-M, Li PK-T, et al. Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am J Hypertens. 2010;23(1):78–84.PubMedCrossRef

11.

Marques FZ, Campain AE, Tomaszewski M, Zukowska-Szczechowska E, Yang YHJ, Charchar FJ, et al. Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension. 2011;58(6):1093–98.PubMedCrossRef

12.

Berthier CC, Bethunaickan R, Gonzalez-Rivera T, Nair V, Ramanujam M, Zhang W, et al. Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis. J Immunol. 2012;189(2):988–1001.PubMedPubMedCentralCrossRef

13.

Warnat P, Eils R, Brors B. Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes. BMC bioinformatics. 2005;6:265.PubMedPubMedCentralCrossRef

14.

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.PubMedPubMedCentralCrossRef

15.

Armstrong RA. When to use the Bonferroni correction. Ophthalmic Physiol Opt. 2014;34(5):502–08.PubMedCrossRef

16.

Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41(Database issue):D808–15.PubMedCrossRef

17.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef

18.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091–3.PubMedPubMedCentralCrossRef

19.

Ramos H, Shannon P, Aebersold R. The protein information and property explorer: an easy-to-use, rich-client web application for the management and functional analysis of proteomic data. Bioinformatics. 2008;24(18):2110–1.PubMedPubMedCentralCrossRef

20.

Ru Y, Kechris KJ, Tabakoff B, Hoffman P, Radcliffe RA, Bowler R, et al. The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res. 2014;42(17):e133.PubMedPubMedCentralCrossRef

21.

Werck-Reichhart D, Feyereisen R. Cytochromes P450: a success story. Genome Biol. 2000;1(6):1–9.CrossRef

22.

Theken KN, Deng Y, Kannon MA, Miller TM, Poloyac SM, Lee CR. Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. Drug Metab Dispos. 2011;39(1):22–9.PubMedPubMedCentralCrossRef

23.

Daemen MA, De VB, Buurman WA. Apoptosis and inflammation in renal reperfusion injury. Transplantation. 2002;73(11):1693–700.PubMedCrossRef

24.

Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S. Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine. Br J Clin Pharmacol. 1997;43(3):245–52.PubMedPubMedCentralCrossRef

25.

Bhatnagar V, Garcia EP, O’Connor DT, Brophy VH, Alcaraz J, Richard E, et al. CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol. 2010;31(2):95–103.PubMedCrossRef

26.

Tsujimoto M, Nagano Y, Hosoda S, Shiraishi A, Miyoshi A, Hiraoka S, et al. Effects of decreased vitamin D and accumulated uremic toxin on human CYP3A4 activity in patients with end-stage renal disease. Toxins. 2013;5(8):1475–85.PubMedPubMedCentralCrossRef

27.

Williams JM, Sharma M, Anjaiahh S, Falck JR, Roman RJ. Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier. Am J Physiol Ren Physiol. 2007;293(2):F501–F05.CrossRef

28.

Fan F, Muroya Y, Roman RJ. Cytochrome P450 eicosanoids in hypertension and renal disease. Curr Opin Nephrol Hypertens. 2015;24(1):37.PubMedCrossRef

29.

Liang J, Yan M, Yang L, Suyila Q, Cui H, Su X. Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China. Genet Mol Res. 2014;13:508–17.PubMedCrossRef

30.

Elijovich F, Laffer CL. The relationship between CYP4A11 and human hypertension. J Hypertens. 2008;26(8):1712–14.PubMedCrossRef

31.

Aguado-Fraile E, Ramos E, Conde E, Rodríguez M, Martín-Gómez L, Lietor A, et al. A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury. PLoS One. 2015;10(6):e0127175.PubMedPubMedCentralCrossRef

32.

Su X, Lee L, Li X, Lv J, Hu Y, Zhan S, et al. Association between angiotensinogen, angiotensin II receptor genes, and blood pressure response to an angiotensin-converting enzyme inhibitor. Circulation. 2007;115(6):725–32.PubMedCrossRef

33.

Valencia DM, Naranjo CA, Parra MV, Caro MA, Valencia AV, Jaramillo CJ, et al. Association and interaction of AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R and PTGS2 genes on the risk of hypertension in Antioquian population. Biomedica. 2013;33(4):598–614.PubMedCrossRef

34.

Sun Y, Liao Y, Yuan Y, Feng L, Ma S, Wei F, et al. Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial. J Am Soc Hypertens. 2014;8(1):21–7.PubMedCrossRef

35.

Henderson SO, Haiman CA, Mack W. Multiple Polymorphisms in the renin- angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort. Am J Med Sci. 2004;328(5):266–73.PubMedCrossRef

36.

Smilde TD, Zuurman MW, Hillege HL, van Veldhuisen DJ, van Gilst WH, van der Steege G, et al. Renal function dependent association of AGTR1 polymorphism (A1166C) and electrocardiographic left-ventricular hypertrophy. Am J Hypertens. 2007;20(10):1097–103.PubMedCrossRef

37.

Campbell CY, Fang BF, Guo X, Peralta CA, Psaty BM, Rich SS, et al. Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the Multi-ethnic Study of Atherosclerosis. Am J Nephrol. 2010;32(2):156–62.PubMedPubMedCentralCrossRef

38.

Durvasula RV, Shankland SJ. The renin-angiotensin system in glomerular podocytes: mediator of glomerulosclerosis and link to hypertensive nephropathy. Curr Hypertens Rep. 2006;8(2):132–38.PubMedCrossRef

39.

Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124(12):1370–81.PubMedCrossRef

40.

Li L, Huang L, Sung SSJ, Vergis AL, Rosin DL, Jr CER, et al. The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia–reperfusion injury. Kidney Int. 2008;74(12):1526–37.PubMedPubMedCentralCrossRef

Title: Identification of potential candidate genes for hypertensive nephropathy based on gene expression profile
Authors: Zhi Chen
Hao Wu
Guohua Wang
Ye Feng
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-016-0366-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Identification of potential candidate genes for hypertensive nephropathy based on gene expression profile

Abstract

Background

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2016

Long term evolution of endothelial function during kidney transplantation

Functional impairment is associated with an increased risk of mortality in patients on chronic hemodialysis

Association between lower serum bicarbonate and renal hyperfiltration in the general population with preserved renal function: a cross-sectional study

Prospective, multicenter, controlled study of quality of life, psychological adjustment process and medical outcomes of patients receiving a preemptive kidney transplant compared to a similar population of recipients after a dialysis period of less than three years – The PreKit-QoL study protocol

Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism

Mortality and illicit drug dependence among hemodialysis patients in the United States: a retrospective cohort analysis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page