Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

Wang,Hui; Wang,Zhengxia; Tang,Qingbin

doi:10.3892/etm.2018.6655

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

Authors:
- Hui Wang
- Zhengxia Wang
- Qingbin Tang
View Affiliations

Affiliations: Department of Endocrinology, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, P.R. China, Clinical Skills Center, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, P.R. China, Emergency Medicine Department, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, P.R. China
Published online on: August 24, 2018 https://doi.org/10.3892/etm.2018.6655
Pages: 3639-3645

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the function and mechanism of action of microRNA (miRNA or miR)‑199a‑3p in vascular endothelial cell injury induced by type 2 diabetes mellitus (T2DM). A total of 36 patients with T2DM (26 males and 10 females; mean age, 52.5±7.0 years) and 20 healthy subjects (10 males and 10 females; mean age, 55.6±4.5 years) were included in the present study. Peripheral blood samples were obtained from all participants and total RNA was extracted Reverse transcription‑quantitative polymerase chain reaction was performed to determine the expression of miR‑199a‑3p. Following the transfection of human umbilical vein endothelial cells (HUVECs) with a negative control (NC) miRNA or miR‑199a‑3p mimics, cell proliferation was assessed using a Cell Counting kit‑8 assay. Cell migration was investigated using Transwell assays and flow cytometry was performed to detect the apoptosis of HUVECs. HUVECs were infected with Ad‑GFP‑LC3B and laser‑scanning confocal microscopy was performed to observe autophagosomes in HUVECs. Western blotting was used to measure the expression of proteins associated with autophagy and the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)‑κB signaling pathway. MiR‑199a‑3p was downregulated in peripheral blood from patients with T2DM compared with healthy subjects. Transfection with miR‑199a‑3p mimics promoted the proliferation and migration of HUVECs. However, miR‑199a‑3p overexpression inhibited the apoptosis of HUVECs. MiR‑199a‑3p facilitated HUVEC autophagy by affecting autophagy‑associated signaling pathways. Furthermore, miR‑199a‑3p regulated the biological functions of HUVECs via the PI3K/AKT/NF‑κB signaling pathway. The results of the present study suggest that miR‑199a‑3p expression was reduced in patients with T2DM compared with healthy subjects and may be associated with vascular endothelial cell injury. In addition, miR‑199a‑3p promoted the proliferation, migration and autophagy of HUVECs, potentially by regulating the PI3K/AKT/NF‑κB signaling pathway. Therefore, miR‑199a‑3p may function as protector of vascular endothelia.

View Figures

View References

1	Buraczynska M, Buraczynska K, Zukowski P and Ksiazek A: Interleukin-4 gene intron 3 VNTR polymorphism in type 2 diabetes patients with peripheral neuropathy. Immunol Invest. 47:146–153. 2018. View Article : Google Scholar : PubMed/NCBI
2	Vernstrom L, Funck KL, Grove EL, Laugesen E, Baier JM, Hvas AM and Poulsen PL: Antiplatelet effect of aspirin during 24h in patients with type 2 diabetes without cardiovascular disease. Thromb Res. 161:1–6. 2018. View Article : Google Scholar : PubMed/NCBI
3	Zhou ZW, Ju HX, Sun MZ, Chen HM, Fu QP and Jiang DM: Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus. Clin Chim Acta. 476:98–102. 2018. View Article : Google Scholar : PubMed/NCBI
4	Iciek R, Brazert M, Wender-Ozegowska E, Pietryga M and Brazert J: Low placental visfatin expression is related to impaired glycaemic control and fetal macrosmia in pregnancies complicated by type 1 diabetes. J Physiol Pharmacol. 69:61–66. 2018.PubMed/NCBI
5	Plessas A, Robertson DP and Hodge PJ: Radiographic bone loss in a Scottish non-smoking Type 1 Diabetes mellitus population; a Bitewing Radiographic Study. J Periodontol. May 15–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
6	Cottam A, Cottam D, Zaveri H, Cottam S, Surve A, Medlin W and Richards C: An analysis of mid-term complications, weight loss, and type 2 diabetes resolution of stomach intestinal pylorus-sparing surgery (SIPS) versus Roux-En-Y gastric bypass (RYGB) with three-year follow-up. Obes Surg. May 22–2018.(Epub ahead of print). View Article : Google Scholar
7	Del Prato S and Chilton R: Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors. Diabetes Obes Metab. 20:786–799. 2018. View Article : Google Scholar : PubMed/NCBI
8	Suchkova OV, Gurfinkel YI and Sasonko ML: Microcirculatory parameters in compensated and decompensated type 2 diabetes mellitus. Ter Arkh. 89:28–35. 2017.(In Russian; Abstract available in Russian from the publisher). View Article : Google Scholar : PubMed/NCBI
9	Nakamura H, Kato M, Nakaya T, Kono M, Tanimura S, Sato T, Fujieda Y, Oku K, Ohira H, Bohgaki T, et al: Decreased haptoglobin levels inversely correlated with pulmonary artery pressure in patients with pulmonary arterial hypertension: A cross-sectional study. Medicine (Baltimore). 96:e83492017. View Article : Google Scholar : PubMed/NCBI
10	Blanco PJ, Muller LO and Spence JD: Blood pressure gradients in cerebral arteries: A clue to pathogenesis of cerebral small vessel disease. Stroke Vasc Neurol. 2:108–117. 2017. View Article : Google Scholar : PubMed/NCBI
11	Li X, Hou J, Du J, Feng J, Yang Y, Shen Y, Chen S, Feng J, Yang D, Pei H, et al: Potential protective mechanism in the cardiac microvascular injury. Hypertension. 72:116–127. 2018. View Article : Google Scholar : PubMed/NCBI
12	Xu X, Cao L, Zhang Y, Lian H, Sun Z and Cui Y: MicroRNA-1246 inhibits cell invasion and epithelial mesenchymal transition process by targeting CXCR4 in lung cancer cells. Cancer Biomark. 21:251–260. 2018. View Article : Google Scholar : PubMed/NCBI
13	Tesfaye D, Gebremedhn S, Salilew-Wondim D, Hailay T, Hoelker M, Grosse-Brinkhaus C and Schellander K: MicroRNAs: Tiny molecules with significant role in mammalian follicular and oocyte development. Reproduction. 155:R121–R135. 2018. View Article : Google Scholar : PubMed/NCBI
14	Liu Y, He X, Li Y and Wang T: Cerebrospinal fluid CD4+ T lymphocyte-derived miRNA-let-7b can enhances the diagnostic performance of Alzheimer's disease biomarkers. Biochem Biophys Res Commun. 495:1144–1150. 2018. View Article : Google Scholar : PubMed/NCBI
15	Lv G, Zhu H, Li C, Wang J, Zhao D, Li S, Ma L, Sun G, Li F, Zhao Y and Gao Y: Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis. Oncotarget. 8:88043–88058. 2017. View Article : Google Scholar : PubMed/NCBI
16	Wang HH, Sun PF, Chen WK, Zhong J, Shi QQ, Weng ML, Ma D and Miao CH: High glucose stimulates expression of MFHAS1 to mitigate inflammation via Akt/HO-1 pathway in human umbilical vein endothelial cells. Inflammation. 41:400–408. 2018. View Article : Google Scholar : PubMed/NCBI
17	Bartoszewski R, Serocki M, Janaszak-Jasiecka A, Bartoszewska S, Kochan-Jamrozy K, Piotrowski A, Króliczewski J and Collawn JF: miR-200b downregulates Kruppel Like Factor 2 (KLF2) during acute hypoxia in human endothelial cells. Eur J Cell Biol. 96:758–766. 2017. View Article : Google Scholar : PubMed/NCBI
18	Zhang HW, Li H, Yan H and Liu BL: MicroRNA-142 promotes the expression of eNOS in human peripheral blood-derived endothelial progenitor cells in vitro. Eur Rev Med Pharmacol Sci. 20:4167–4175. 2016.PubMed/NCBI
19	Varshney A, Panda JJ, Singh AK, Yadav N, Bihari C, Biswas S, Sarin SK and Chauhan VS: Targeted delivery of microRNA-199a-3p using self-assembled dipeptide nanoparticles efficiently reduces hepatocellular carcinoma in mice. Hepatology. 67:1392–1407. 2018. View Article : Google Scholar : PubMed/NCBI
20	Qu F, Zheng J, Gan W, Lian H, He H, Li W, Yuan T, Yang Y, Li X, Ji C, et al: MiR-199a-3p suppresses proliferation and invasion of prostate cancer cells by targeting Smad1. Oncotarget. 8:52465–52473. 2017. View Article : Google Scholar : PubMed/NCBI
21	Park KM, Teoh JP, Wang Y, Broskova Z, Bayoumi AS, Tang Y, Su H, Weintraub NL and Kim IM: Carvedilol-responsive microRNAs, miR-199a-3p and −214 protect cardiomyocytes from simulated ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 311:H371–H383. 2016. View Article : Google Scholar : PubMed/NCBI
22	Zhu H and Leung SW: Identification of microRNA biomarkers in type 2 diabetes: A meta-analysis of controlled profiling studies. Diabetologia. 58:900–911. 2015. View Article : Google Scholar : PubMed/NCBI
23	Mathews E, Thomas E, Absetz P, D'Esposito F, Aziz Z, Balachandran S, Daivadanam M, Thankappan KR and Oldenburg B: Cultural adaptation of a peer-led lifestyle intervention program for diabetes prevention in India: The Kerala diabetes prevention program (K-DPP). BMC Public Health. 17:9742018. 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	Coelho SC, Berillo O, Caillon A, Ouerd S, Fraulob-Aquino JC, Barhoumi T, Offermanns S, Paradis P and Schiffrin EL: Three-month endothelial human endothelin-1 overexpression causes blood pressure elevation and vascular and kidney injury. Hypertension. 71:208–216. 2018. View Article : Google Scholar : PubMed/NCBI
26	Lai TS, Lindberg RA, Zhou HL, Haroon ZA, Dewhirst MW, Hausladen A, Juang YL, Stamler JS and Greenberg CS: Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide. Sci Rep. 7:161632017. View Article : Google Scholar : PubMed/NCBI
27	Pang LP, Li Y, Zou QY, Zhou C, Lei W, Zheng J and Huang SA: ITE inhibits growth of human pulmonary artery endothelial cells. Exp Lung Res. 43:283–292. 2017. View Article : Google Scholar : PubMed/NCBI
28	Yang X, He XQ, Li GD and Xu YQ: AntagomiR-451 inhibits oxygen glucose deprivation (OGD)-induced HUVEC necrosis via activating AMPK signaling. PLoS One. 12:e01755072017. View Article : Google Scholar : PubMed/NCBI
29	Howe GA, Kazda K and Addison CL: MicroRNA-30b controls endothelial cell capillary morphogenesis through regulation of transforming growth factor beta 2. PLoS One. 12:e01856192017. View Article : Google Scholar : PubMed/NCBI
30	Chen Z, Wang M, He Q, Li Z, Zhao Y, Wang W, Ma J, Li Y and Chang G: MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1. Exp Ther Med. 13:1702–1710. 2017. View Article : Google Scholar : PubMed/NCBI
31	Sun JY, Zhao ZW, Li WM, Yang G, Jing PY, Li P, Dang HZ, Chen Z, Zhou YA and Li XF: Knockdown of MALAT1 expression inhibits HUVEC proliferation by upregulation of miR-320a and downregulation of FOXM1 expression. Oncotarget. 8:61499–61509. 2017.PubMed/NCBI
32	Lin SY, Hsieh SY, Fan YT, Wei WC, Hsiao PW, Tsai DH, Wu TS and Yang NS: Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance. Autophagy. 14:778–795. 2018. View Article : Google Scholar : PubMed/NCBI
33	Yuan Y, Li X and Li M: Overexpression of miR-17-5p protects against high glucose-induced endothelial cell injury by targeting E2F1-mediated suppression of autophagy and promotion of apoptosis. Int J Mol Med. May 21–2018.(Epub ahead of print). View Article : Google Scholar
34	Chao CH, Chen HR, Chuang YC and Yeh TM: Macrophage migration inhibitory factor-induced autophagy contributes to thrombin-triggered endothelial hyperpermeability in sepsis. Shock. 50:103–111. 2018. View Article : Google Scholar : PubMed/NCBI
35	Zhang Y, Sun J, Yu X, Shi L, Du W, Hu L, Liu C and Cao Y: SIRT1 regulates accumulation of oxidized LDL in HUVEC via the autophagy-lysosomal pathway. Prostaglandins Other Lipid Mediat. 122:37–44. 2016. View Article : Google Scholar : PubMed/NCBI
36	Fan H, Ma X, Lin P, Kang Q, Zhao Z, Wang L, Sun D, Cheng J and Li Y: Scutellarin prevents nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia via PI3K/AKT-dependent activation of nuclear factor (Erythroid-Derived 2)-like 2 (Nrf2) in rats. Med Sci Monit. 23:5599–5612. 2017. View Article : Google Scholar : PubMed/NCBI
37	Liu LT, Liang L, Wang W, Yan CQ, Zhang J, Xiao YC, Ye L, Zhao MX, Huang QS, Bian JJ, et al: Isolariciresinol-9′-O-α-L-arabinofuranoside protects against hydrogen peroxideinduced apoptosis of human umbilical vein endothelial cells via a PI3K/Akt/Bad-dependent pathway. Mol Med Rep. 17:488–494. 2018.PubMed/NCBI
38	Xing Y, Lai J, Liu X, Zhang N, Ming J, Liu H and Zhang X: Netrin-1 restores cell injury and impaired angiogenesis in vascular endothelial cells upon high glucose by PI3K/AKT-eNOS. J Mol Endocrinol. 58:167–177. 2017. View Article : Google Scholar : PubMed/NCBI
39	Chu P, Han G, Ahsan A, Sun Z, Liu S, Zhang Z, Sun B, Song Y, Lin Y, Peng J and Tang Z: Phosphocreatine protects endothelial cells from methylglyoxal induced oxidative stress and apoptosis via the regulation of PI3K/Akt/eNOS and NF-κB pathway. Vascul Pharmacol. 91:26–35. 2017. View Article : Google Scholar : PubMed/NCBI