Overexpression of MiR-34c Inhibits High Glucose-induced Apoptosis in Podocytes by Targeting Notch Signaling Pathways

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Jul 21

PMID 26191142

Citations 34

Authors

Xiang-Dong Liu

Lian-Yun Zhang

Tie-Chui Zhu

Rui-Fang Zhang

Shu-Long Wang

Yan Bao

Affiliations

Soon will be listed here.

Abstract

Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.

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References

Mendell J, Olson E . MicroRNAs in stress signaling and human disease. Cell. 2012; 148(6):1172-87. PMC: 3308137. DOI: 10.1016/j.cell.2012.02.005. View

Liu L, Gao C, Chen G, Li X, Li J, Wan Q . Notch Signaling Molecules Activate TGF- β in Rat Mesangial Cells under High Glucose Conditions. J Diabetes Res. 2013; 2013:979702. PMC: 3652152. DOI: 10.1155/2013/979702. View

Samon J, Champhekar A, Minter L, Telfer J, Miele L, Fauq A . Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood. 2008; 112(5):1813-21. PMC: 2518888. DOI: 10.1182/blood-2008-03-144980. View

Lin C, Wang F, Hsu Y, Chen C, Tseng M, Saleem M . Modulation of notch-1 signaling alleviates vascular endothelial growth factor-mediated diabetic nephropathy. Diabetes. 2010; 59(8):1915-25. PMC: 2911050. DOI: 10.2337/db09-0663. View

Bonegio R, Susztak K . Notch signaling in diabetic nephropathy. Exp Cell Res. 2012; 318(9):986-92. PMC: 3677813. DOI: 10.1016/j.yexcr.2012.02.036. View

Walsh D, Roxburgh S, McGettigan P, Berthier C, Higgins D, Kretzler M . Co-regulation of Gremlin and Notch signalling in diabetic nephropathy. Biochim Biophys Acta. 2007; 1782(1):10-21. DOI: 10.1016/j.bbadis.2007.09.005. View

Yoon K, Lee J, Kim J, Cho J, Choi Y, Ko S . Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006; 368(9548):1681-8. DOI: 10.1016/S0140-6736(06)69703-1. View

Hilton M, Tu X, Wu X, Bai S, Zhao H, Kobayashi T . Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med. 2008; 14(3):306-14. PMC: 2740725. DOI: 10.1038/nm1716. View

Bae Y, Yang T, Zeng H, Campeau P, Chen Y, Bertin T . miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet. 2012; 21(13):2991-3000. PMC: 3373245. DOI: 10.1093/hmg/dds129. View

10.

Chen J, Gui D, Chen Y, Mou L, Liu Y, Huang J . Astragaloside IV improves high glucose-induced podocyte adhesion dysfunction via alpha3beta1 integrin upregulation and integrin-linked kinase inhibition. Biochem Pharmacol. 2008; 76(6):796-804. DOI: 10.1016/j.bcp.2008.06.020. View

11.

Gao F, Yao M, Shi Y, Hao J, Ren Y, Liu Q . Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl-2 and p53 pathways. J Cell Biochem. 2012; 114(5):1029-38. DOI: 10.1002/jcb.24442. View

12.

Long J, Wang Y, Wang W, Chang B, Danesh F . Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem. 2010; 285(30):23457-65. PMC: 2906336. DOI: 10.1074/jbc.M110.136168. View

13.

Li C, Xia M, Han W, Li X, Zhang C, Boini K . Reversal by growth hormone of homocysteine-induced epithelial-to-mesenchymal transition through membrane raft-redox signaling in podocytes. Cell Physiol Biochem. 2011; 27(6):691-702. PMC: 3221271. DOI: 10.1159/000330078. View

14.

Hagman Z, Larne O, Edsjo A, Bjartell A, Ehrnstrom R, Ulmert D . miR-34c is downregulated in prostate cancer and exerts tumor suppressive functions. Int J Cancer. 2011; 127(12):2768-76. DOI: 10.1002/ijc.25269. View

15.

Saleem M, OHare M, Reiser J, Coward R, Inward C, Farren T . A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol. 2002; 13(3):630-638. DOI: 10.1681/ASN.V133630. View

16.

Morizane R, Fujii S, Monkawa T, Hiratsuka K, Yamaguchi S, Homma K . miR-34c attenuates epithelial-mesenchymal transition and kidney fibrosis with ureteral obstruction. Sci Rep. 2014; 4:4578. PMC: 3974136. DOI: 10.1038/srep04578. View

17.

Nakai S, Masakane I, Akiba T, Shigematsu T, Yamagata K, Watanabe Y . Overview of regular dialysis treatment in Japan as of 31 December 2006. Ther Apher Dial. 2009; 12(6):428-56. DOI: 10.1111/j.1744-9987.2008.00634.x. View

18.

Catuogno S, Cerchia L, Romano G, Pognonec P, Condorelli G, de Franciscis V . miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis. Oncogene. 2012; 32(3):341-51. DOI: 10.1038/onc.2012.51. View

19.

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

20.

Lim J, Lim S, Park M, Kim G, Han H, Park S . Cannabinoid receptor 1 mediates high glucose-induced apoptosis via endoplasmic reticulum stress in primary cultured rat mesangial cells. Am J Physiol Renal Physiol. 2011; 301(1):F179-88. DOI: 10.1152/ajprenal.00032.2010. View