Renal Medullary MicroRNAs in Dahl Salt-sensitive Rats: MiR-29b Regulates Several Collagens and Related Genes

Overview

Journal Hypertension

Date 2010 Mar 3

PMID 20194304

Citations 144

Authors

Yong Liu

Norman E Taylor

Limin Lu

Kristie Usa

Allen W Cowley Jr

Nicholas R Ferreri

Nan Cher Yeo

Mingyu Liang

Affiliations

Soon will be listed here.

Abstract

MicroRNAs are endogenous repressors of gene expression. We examined microRNAs in the renal medulla of Dahl salt-sensitive rats and consomic SS-13(BN) rats. Salt-induced hypertension and renal injury in Dahl salt-sensitive rats, particularly medullary interstitial fibrosis, have been shown previously to be substantially attenuated in SS-13(BN) rats. Of 377 microRNAs examined, 5 were found to be differentially expressed between Dahl salt-sensitive rats and consomic SS-13(BN) rats receiving a high-salt diet. Real-time PCR analysis demonstrated that high-salt diets induced substantial upregulation of miR-29b in the renal medulla of SS-13(BN) rats but not in SS rats. miR-29b was predicted to regulate 20 collagen genes, matrix metalloproteinase 2 (Mmp2), integrin beta1 (Itgb1), and other genes related to the extracellular matrix. Expression of 9 collagen genes and Mmp2 was upregulated by a high-salt diet in the renal medulla of SS rats, but not in SS-13(BN) rats, an expression pattern opposite to miR-29b. Knockdown of miR-29b in the kidneys of SS-13(BN) rats resulted in upregulation of several collagen genes. miR-29b reduced expression levels of several collagen genes and Itgb1 in cultured rat renal medullary epithelial cells. Moreover, miR-29b suppressed the activity of luciferase when the reporter gene was linked to a 3'-untranslated segment of collagen genes Col1a1, Col3a1, Col4a1, Col5a1, Col5a2, Col5a3, Col7a1, Col8a1, Mmp2, or Itgb1 but not Col12a1. The result demonstrated broad effects of miR-29b on a large number of collagens and genes related to the extracellular matrix and suggested involvement of miR-29b in the protection from renal medullary injury in SS-13(BN) rats.

Citing Articles

MicroRNAs in diabetes mellitus.

Shaik Syed Ali P, Ahmad M, Parveen K J Diabetes Metab Disord. 2025; 24(1):77.

PMID: 40060270 PMC: 11885724. DOI: 10.1007/s40200-025-01591-y.

Associations of microRNA Gene Polymorphisms With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Hypertension Incidence in the Chinese Population.

Zhang X, Yao S, Wang Y, Chu C, Du M, Mu J J Clin Hypertens (Greenwich). 2025; 27(2):e70019.

PMID: 39994918 PMC: 11850435. DOI: 10.1111/jch.70019.

microRNA and Hypertension.

He L, Liu Y, Widlansky M, Kriegel A, Qiu Q, Liang M Hypertension. 2024; 82(2):181-184.

PMID: 39633557 PMC: 11893092. DOI: 10.1161/HYPERTENSIONAHA.124.21728.

Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys.

Jain A, Jung H, Aubee J, ONeil J, Muhammad L, Khan S Biomolecules. 2024; 14(9).

PMID: 39334814 PMC: 11430241. DOI: 10.3390/biom14091048.

Potential of Modulating Aldosterone Signaling and Mineralocorticoid Receptor with microRNAs to Attenuate Diabetic Kidney Disease.

Hagiwara S, Gohda T, Kantharidis P, Okabe J, Murakoshi M, Suzuki Y Int J Mol Sci. 2024; 25(2).

PMID: 38255942 PMC: 10815168. DOI: 10.3390/ijms25020869.

References

Naraba H, Iwai N . Assessment of the microRNA system in salt-sensitive hypertension. Hypertens Res. 2006; 28(10):819-26. DOI: 10.1291/hypres.28.819. View

Harvey S, Jarad G, Cunningham J, Goldberg S, Schermer B, Harfe B . Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J Am Soc Nephrol. 2008; 19(11):2150-8. PMC: 2573015. DOI: 10.1681/ASN.2008020233. View

Sengupta S, den Boon J, Chen I, Newton M, Stanhope S, Cheng Y . MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A. 2008; 105(15):5874-8. PMC: 2311339. DOI: 10.1073/pnas.0801130105. View

Prockop D, Kivirikko K . Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem. 1995; 64:403-34. DOI: 10.1146/annurev.bi.64.070195.002155. View

Liang M, Yuan B, Rute E, Greene A, Zou A, Soares P . Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study. Physiol Genomics. 2002; 8(2):139-49. DOI: 10.1152/physiolgenomics.00083.2001. View

Eulalio A, Huntzinger E, Izaurralde E . Getting to the root of miRNA-mediated gene silencing. Cell. 2008; 132(1):9-14. DOI: 10.1016/j.cell.2007.12.024. View

Taylor N, Glocka P, Liang M, Cowley Jr A . NADPH oxidase in the renal medulla causes oxidative stress and contributes to salt-sensitive hypertension in Dahl S rats. Hypertension. 2006; 47(4):692-8. DOI: 10.1161/01.HYP.0000203161.02046.8d. View

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

Cowley Jr A . The genetic dissection of essential hypertension. Nat Rev Genet. 2006; 7(11):829-40. DOI: 10.1038/nrg1967. View

10.

Liu Y, Park F, Pietrusz J, Jia G, Singh R, Netzel B . Suppression of 11beta-hydroxysteroid dehydrogenase type 1 with RNA interference substantially attenuates 3T3-L1 adipogenesis. Physiol Genomics. 2007; 32(3):343-51. DOI: 10.1152/physiolgenomics.00067.2007. View

11.

Martin M, Lee E, Buckenberger J, Schmittgen T, Elton T . MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J Biol Chem. 2006; 281(27):18277-84. DOI: 10.1074/jbc.M601496200. View

12.

Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi J . MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A. 2007; 104(9):3432-7. PMC: 1805579. DOI: 10.1073/pnas.0611192104. View

13.

RAPP J . Dahl salt-susceptible and salt-resistant rats. A review. Hypertension. 1982; 4(6):753-63. DOI: 10.1161/01.hyp.4.6.753. View

14.

Tian Z, Greene A, Usa K, Matus I, Bauwens J, Pietrusz J . Renal regional proteomes in young Dahl salt-sensitive rats. Hypertension. 2008; 51(4):899-904. DOI: 10.1161/HYPERTENSIONAHA.107.109173. View

15.

Morrison J, Knoll K, Hessner M, Liang M . Effect of high glucose on gene expression in mesangial cells: upregulation of the thiol pathway is an adaptational response. Physiol Genomics. 2004; 17(3):271-82. DOI: 10.1152/physiolgenomics.00031.2004. View

16.

Ho J, Ng K, Rosen S, Dostal A, Gregory R, Kreidberg J . Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol. 2008; 19(11):2069-75. PMC: 2573018. DOI: 10.1681/ASN.2008020162. View

17.

Rajewsky N . microRNA target predictions in animals. Nat Genet. 2006; 38 Suppl:S8-13. DOI: 10.1038/ng1798. View

18.

Makeyev E, Maniatis T . Multilevel regulation of gene expression by microRNAs. Science. 2008; 319(5871):1789-90. PMC: 3139454. DOI: 10.1126/science.1152326. View

19.

Liang M, Lee N, Wang H, Greene A, Kwitek A, Kaldunski M . Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats. Physiol Genomics. 2008; 34(1):54-64. DOI: 10.1152/physiolgenomics.00031.2008. View

20.

Liang M, Yuan B, Rute E, Greene A, Olivier M, Cowley Jr A . Insights into Dahl salt-sensitive hypertension revealed by temporal patterns of renal medullary gene expression. Physiol Genomics. 2002; 12(3):229-37. DOI: 10.1152/physiolgenomics.00089.2002. View