RAAV9-mediated Supplementation of MiR-29b Improve Angiotensin-II Induced Renal Fibrosis in Mice

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2021 Aug 19

PMID 34407760

Citations 4

Authors

Ju-Hong Zhang

Jing Li

Yang Ye

Wang-Qi Yu

Affiliations

Soon will be listed here.

Abstract

Background: Renin-angiotensin-aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction.

Method: Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology.

Results: In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b.

Conclusion: Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury.

Citing Articles

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Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-β/smad signaling pathway.

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Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients.

Chen Y, Hsu C, Tsai S, Chen C Int J Mol Sci. 2022; 23(20).

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Cai Y, Feng Z, Jia Q, Guo J, Zhang P, Zhao Q Front Pharmacol. 2022; 12:801094.

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References

Kriegel A, Liu Y, Fang Y, Ding X, Liang M . The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury. Physiol Genomics. 2012; 44(4):237-44. PMC: 3289120. DOI: 10.1152/physiolgenomics.00141.2011. View

Almeida L, Tofteng S, Madsen K, Jensen B . Role of the renin-angiotensin system in kidney development and programming of adult blood pressure. Clin Sci (Lond). 2020; 134(6):641-656. DOI: 10.1042/CS20190765. View

DuPont J, McCurley A, Davel A, McCarthy J, Bender S, Hong K . Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging. JCI Insight. 2016; 1(14):e88942. PMC: 5033871. DOI: 10.1172/jci.insight.88942. View

Xiong M, Jiang L, Zhou Y, Qiu W, Fang L, Tan R . The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression. Am J Physiol Renal Physiol. 2011; 302(3):F369-79. DOI: 10.1152/ajprenal.00268.2011. View

Pan J, Zhang J, Zhang X, Zhou X, Lu S, Huang X . Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells. Int J Mol Med. 2014; 34(5):1381-7. DOI: 10.3892/ijmm.2014.1935. View

Valls-Lacalle L, Negre-Pujol C, Rodriguez C, Varona S, Valera-Canellas A, Consegal M . Opposite Effects of Moderate and Extreme Cx43 Deficiency in Conditional Cx43-Deficient Mice on Angiotensin II-Induced Cardiac Fibrosis. Cells. 2019; 8(10). PMC: 6830333. DOI: 10.3390/cells8101299. View

Zeisberg M, Neilson E . Mechanisms of tubulointerstitial fibrosis. J Am Soc Nephrol. 2010; 21(11):1819-34. DOI: 10.1681/ASN.2010080793. View

Schievenbusch S, Strack I, Scheffler M, Nischt R, Coutelle O, Hosel M . Combined paracrine and endocrine AAV9 mediated expression of hepatocyte growth factor for the treatment of renal fibrosis. Mol Ther. 2010; 18(7):1302-9. PMC: 2911253. DOI: 10.1038/mt.2010.71. View

Shen X, Xu Y, Bai Z, Ma D, Niu Q, Meng J . Transparenchymal Renal Pelvis Injection of Recombinant Adeno-Associated Virus Serotype 9 Vectors Is a Practical Approach for Gene Delivery in the Kidney. Hum Gene Ther Methods. 2018; 29(6):251-258. DOI: 10.1089/hgtb.2018.148. View

10.

Bretschneider M, Busch B, Mueller D, Nolze A, Schreier B, Gekle M . Activated mineralocorticoid receptor regulates micro-RNA-29b in vascular smooth muscle cells. FASEB J. 2016; 30(4):1610-22. DOI: 10.1096/fj.15-271254. View

11.

Chen H . Exploiting the Intron-splicing Mechanism of Insect Cells to Produce Viral Vectors Harboring Toxic Genes for Suicide Gene Therapy. Mol Ther Nucleic Acids. 2012; 1:e57. PMC: 3511675. DOI: 10.1038/mtna.2012.48. View

12.

Liu Y, Taylor N, Lu L, Usa K, Cowley Jr A, Ferreri N . Renal medullary microRNAs in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes. Hypertension. 2010; 55(4):974-82. PMC: 2862728. DOI: 10.1161/HYPERTENSIONAHA.109.144428. View

13.

Haghikia A, Hoch M, Stapel B, Hilfiker-Kleiner D . STAT3 regulation of and by microRNAs in development and disease. JAKSTAT. 2013; 1(3):143-50. PMC: 3670237. DOI: 10.4161/jkst.19573. View

14.

Van Rooij E, Sutherland L, Thatcher J, DiMaio J, Naseem R, Marshall W . Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A. 2008; 105(35):13027-32. PMC: 2529064. DOI: 10.1073/pnas.0805038105. View