miR-200c serves an important role in H5V endothelial cells in high glucose by targeting Notch1

Zhang,Yunfeng; Guan,Qiang; Jin,Xing

doi:10.3892/mmr.2017.6792

miR-200c serves an important role in H5V endothelial cells in high glucose by targeting Notch1

Authors:
- Yunfeng Zhang
- Qiang Guan
- Xing Jin
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Affiliations: Department of Vascular Surgery, Shanxi People's Hospital, Taiyuan, Shanxi 030012, P.R. China, Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: June 15, 2017 https://doi.org/10.3892/mmr.2017.6792
Pages: 2149-2155

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Abstract

Diabetic vasculopathy is the leading cause of impairment and death in diabetic patients, a variety of factors are involved in its underlying pathological process, however, endothelial cell (EC) dysfunction serves a significant role in the process. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates, due to their ability to regulate multiple targets involved in ECs. The aim of the present study was to investigate the role of miR‑200c in regulating ECs in high glucose condition. To investigate the role of miR‑200c in regulating hyperglycemia induced ECs by targeting Notch1, ECs H5V cells were cultured in high sugar conditions to initiate the inhibition of Notch1, the same cells in normal medium as the control. H5V cells were transfected with miR‑200c mimics, miR‑200c inhibitors or scrambled oligonucleotide controls, respectively. Notch1 and Hes1 mRNA and protein expression level were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The present study reported that miR‑200c was highly expressed by high glucose stimulation in H5V cells, however Notch1 was inhibited by high glucose, and it was also depressed by miR‑200c in high glucose conditions. Notch1 was identified as the target gene of miR‑200c, luciferase reporter assays confirmed the biochemical relationship for miR‑200c decreasing Notch1. The current findings revealed that miR‑200c may inhibit Notch1 expression in high glucose conditions, which suggested that miR‑200c mediating Notch1/Hes1 may involve in the process of vascular damage caused by hyperglycemia.

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1	Fiorentino TV, Prioletta A, Zuo P and Folli F: Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 19:5695–5703. 2013. View Article : Google Scholar : PubMed/NCBI
2	Jeffcoate WJ and Harding KG: Diabetic foot ulcers. Lancet. 361:1545–1551. 2003. View Article : Google Scholar : PubMed/NCBI
3	Chiaramonte R, Basile A, Tassi E, Calzavara E, Cecchinato V, Rossi V, Biondi A and Comi P: A wide role for NOTCH1 signaling in acute leukemia. Cancer Lett. 219:113–120. 2005. View Article : Google Scholar : PubMed/NCBI
4	Hellström M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, et al: Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 445:776–780. 2007. View Article : Google Scholar : PubMed/NCBI
5	Williams CK, Li JL, Murga M, Harris AL and Tosato G: Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood. 107:931–939. 2006. View Article : Google Scholar : PubMed/NCBI
6	Kopan R and Ilagan MX: The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell. 137:216–233. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ishiko E, Matsumura I, Ezoe S, Gale K, Ishiko J, Satoh Y, Tanaka H, Shibayama H, Mizuki M, Era T, et al: Notch signals inhibit the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through the induction of HES1. J Biol Chem. 280:4929–4939. 2005. View Article : Google Scholar : PubMed/NCBI
8	Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD and Srivastava D: Mutations in NOTCH1 cause aortic valve disease. Nature. 437:270–274. 2005. View Article : Google Scholar : PubMed/NCBI
9	Iso T, Kedes L and Hamamori Y: HES and HERP families: Multiple effectors of the Notch signaling pathway. J Cell Physiol. 194:237–255. 2003. View Article : Google Scholar : PubMed/NCBI
10	Liao WR, Hsieh RH, Hsu KW, Wu MZ, Tseng MJ, Mai RT, Wu Lee YH and Yeh TS: The CBF1-independent Notch1 signal pathway activates human c-myc expression partially via transcription factor YY1. Carcinogenesis. 28:1867–1876. 2007. View Article : Google Scholar : PubMed/NCBI
11	Jaiswal MK, Agrawal V, Pamarthy S, Katara GK, Kulshrestha A, Gilman-Sachs A, Beaman KD and Hirsch E: Notch signaling in inflammation-induced preterm labor. Sci Rep. 5:152212015. View Article : Google Scholar : PubMed/NCBI
12	Xie F, Cai W, Liu Y, Li Y, Du B, Feng L and Qiu L: Vaccarin attenuates the human EA.hy926 endothelial cell oxidative stress injury through inhibition of Notch signaling. Int J Mol Med. 35:135–142. 2015.PubMed/NCBI
13	Xi G, Shen X, Wai C, Vilas CK and Clemmons DR: Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF-κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle. FASEB J. 29:4772–4782. 2015. View Article : Google Scholar : PubMed/NCBI
14	Fang Q, Wang J, Wang L, Zhang Y, Yin H, Li Y, Tong C, Liang G and Zheng C: Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice. Toxicol Appl Pharmacol. 288:179–191. 2015. View Article : Google Scholar : PubMed/NCBI
15	Ferrer-Lorente R, Bejar MT and Badimon L: Notch signaling pathway activation in normal and hyperglycemic rats differs in the stem cells of visceral and subcutaneous adipose tissue. Stem Cells Dev. 23:3034–3048. 2014. View Article : Google Scholar : PubMed/NCBI
16	Zhou Y, Gu P, Shi W, Li J, Hao Q, Cao X, Lu Q and Zeng Y: MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells. Int J Mol Med. 37:931–938. 2016.PubMed/NCBI
17	Silambarasan M, Tan JR, Karolina DS, Armugam A, Kaur C and Jeyaseelan K: MicroRNAs in hyperglycemia induced endothelial cell dysfunction. Int J Mol Sci. 17:5182016. View Article : Google Scholar : PubMed/NCBI
18	Ocłoń E, Latacz A, Zubel-Łojek J and Pierzchała-Koziec K: Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets. J Endocrinol. 229:259–266. 2016. View Article : Google Scholar : PubMed/NCBI
19	Magenta A, Cencioni C, Fasanaro P, Zaccagnini G, Greco S, Sarra-Ferraris G, Antonini A, Martelli F and Capogrossi MC: miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition. Cell Death Differ. 18:1628–1639. 2011. View Article : Google Scholar : PubMed/NCBI
20	Luo Z, Wen G, Wang G, Pu X, Ye S, Xu Q, Wang W and Xiao Q: MicroRNA-200C and −150 play an important role in endothelial cell differentiation and vasculogenesis by targeting transcription repressor ZEB1. Stem Cells. 31:1749–1762. 2013. View Article : Google Scholar : PubMed/NCBI
21	Song C, Liu LZ, Pei XQ, Liu X, Yang L, Ye F and Xie X, Chen J, Tang H and Xie X: miR-200c inhibits breast cancer proliferation by targeting KRAS. Oncotarget. 6:34968–34978. 2015.PubMed/NCBI
22	Kumar K, Chow CR, Ebine K, Arslan AD, Kwok B, Bentrem DJ, Eckerdt FD, Platanias LC and Munshi HG: Differential Regulation of ZEB1 and EMT by MAPK-interacting protein kinases (MNKs) and eIF4E in pancreatic cancer. Mol Cancer Res. 14:216–227. 2016. View Article : Google Scholar : PubMed/NCBI
23	Guilini C, Urayama K, Turkeri G, Dedeoglu DB, Kurose H, Messaddeq N and Nebigil CG: Divergent roles of prokineticin receptors in the endothelial cells: Angiogenesis and fenestration. Am J Physiol Heart Circ Physiol. 298:H844–H852. 2010. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Liu S, Ma X, Ai Q, Huang Q, Shi T, Zhu M, Wang B and Zhang X: NOTCH1 functions as an oncogene by regulating the PTEN/PI3K/AKT pathway in clear cell renal cell carcinoma. Urol Oncol. 31:938–948. 2013. View Article : Google Scholar : PubMed/NCBI
26	Zhou Y, Li JS, Zhang X, Wu YJ, Huang K and Zheng L: Ursolic acid inhibits early lesions of diabetic nephropathy. Int J Mol Med. 26:565–570. 2010.PubMed/NCBI