miR‑126 is essential for endothelial phenotype expression during endothelial differentiation in adipose‑derived stem cells

Xie,Han; Wang,Fang; Chen,Xiao; Ying,Hao

doi:10.3892/mmr.2017.7915

miR‑126 is essential for endothelial phenotype expression during endothelial differentiation in adipose‑derived stem cells

Authors:
- Han Xie
- Fang Wang
- Xiao Chen
- Hao Ying
View Affiliations

Affiliations: Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, P.R. China, Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: October 27, 2017 https://doi.org/10.3892/mmr.2017.7915
Pages: 442-446

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 endothelial differentiation of stem cells serves an essential role in vascular development, function and disease. Autograft adipose‑derived stem cells (ADSCs) may be a novel source of cell for use in the study of angiogenesis. microRNA‑126 (miR‑126) has been extensively studied in endothelial cells. However, the effect of miR‑126 on the endothelial differentiation of ADSCs has not been demonstrated. In the present study, it was observed that the expression of miR‑126 was markedly increased during the endothelial differentiation of ADSCs in a time‑dependent manner. The effect of miR‑126 on ADSC differentiation was confirmed by employing up‑ and down‑regulation strategies. The expression of endothelial markers was decreased by miR‑126 inhibitor transfection during endothelial differentiation. The results of the present study suggest that miR‑126 is essential for endothelial phenotype expression, and may promote the progress of endothelial differentiation in ADSCs, providing a novel strategy for modulating vascular formation and function.

View Figures

View References

1	Trounson A and McDonald C: Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell. 17:11–22. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yang Y, Chen XH, Li FG, Chen YX, Gu LQ, Zhu JK and Li P: In vitro induction of human adipose-derived stem cells into lymphatic endothelial-like cells. Cell Reprogram. 17:69–76. 2015. View Article : Google Scholar : PubMed/NCBI
3	Hu F, Wang X, Liang G, Lv L, Zhu Y, Sun B and Xiao Z: Effects of epidermal growth factor and basic fibroblast growth factor on the proliferation and osteogenic and neural differentiation of adipose-derived stem cells. Cell Reprogram. 15:224–232. 2013.PubMed/NCBI
4	De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P, et al: Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 174:101–109. 2003. View Article : Google Scholar : PubMed/NCBI
5	Ikegame Y, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F, Yamada K, Tanaka Y, Egashira Y, Nakashima S, et al: Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy. 13:675–685. 2011. View Article : Google Scholar : PubMed/NCBI
6	Locke M, Feisst V and Dunbar PR: Concise review: Human adipose-derived stem cells: Separating promise from clinical need. Stem Cells. 29:404–411. 2011. View Article : Google Scholar : PubMed/NCBI
7	Khan WS, Adesida AB, Tew SR, Longo UG and Hardingham TE: Fat pad-derived mesenchymal stem cells as a potential source for cell-based adipose tissue repair strategies. Cell Prolif. 45:111–120. 2012. View Article : Google Scholar : PubMed/NCBI
8	Fraser JK, Wulur I, Alfonso Z and Hedrick MH: Fat tissue: An underappreciated source of stem cells for biotechnology. Trends Biotechnol. 24:150–154. 2006. View Article : Google Scholar : PubMed/NCBI
9	Park IS, Rhie JW and Kim SH: A novel three-dimensional adipose-derived stem cell cluster for vascular regeneration in ischemic tissue. Cytotherapy. 16:508–522. 2014. View Article : Google Scholar : PubMed/NCBI
10	Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY and Srivastava D: miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 15:272–284. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R and Olson EN: The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 15:261–271. 2008. View Article : Google Scholar : PubMed/NCBI
12	Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ and Kuo CJ: Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development. 135:3989–3993. 2008. View Article : Google Scholar : PubMed/NCBI
13	Sasahira T, Kurihara M, Bhawal UK, Ueda N, Shimomoto T, Yamamoto K, Kirita T and Kuniyasu H: Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer. Br J Cancer. 107:700–706. 2012. View Article : Google Scholar : PubMed/NCBI
14	Nowak WN, Florczyk U, Józkowicz A and Dulak J: Role of microRNA in endothelial cells-regulation of differentiation and angiogenesis. Postepy Biochem. 59:405–414. 2013.(In Polish). PubMed/NCBI
15	Yan T, Liu Y, Cui K, Hu B, Wang F and Zou L: MicroRNA-126 regulates EPCs function: Implications for a role of miR-126 in preeclampsia. J Cell Biochem. 114:2148–2159. 2013. View Article : Google Scholar : PubMed/NCBI
16	Meister J and Schmidt MH: miR-126 and miR-126*: New players in cancer. ScientificWorldJournal. 10:2090–2100. 2010. View Article : Google Scholar : PubMed/NCBI
17	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
18	Ikegame Y, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F, Yamada K, Tanaka Y, Egashira Y, Nakashima S, et al: Comparison of mesenchymal stem cells from adiposetissue and bonemarrow for ischemicstroke therapy. Cytotherapy. 13:675–685. 2011. View Article : Google Scholar : PubMed/NCBI
19	Nakagami H, Maeda K, Morishita R, Iguchi S, Nishikawa T, Takami Y, Kikuchi Y, Saito Y, Tamai K, Ogihara T and Kaneda Y: Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells. Arterioscler Thromb Vasc Biol. 25:2542–2547. 2005. View Article : Google Scholar : PubMed/NCBI
20	Su SJ, Yeh YT, Su SH, Chang KL, Shyu HW, Chen KM and Yeh H: Biochanin a promotes osteogenic but inhibits adipogenic differentiation: Evidence with primary adipose-derived stem cells. Evid Based Complement Alternat Med. 2013:8460392013. View Article : Google Scholar : PubMed/NCBI
21	Wu Z, Yin H, Liu T, Yan W, Li Z, Chen J, Chen H, Wang T, Jiang Z, Zhou W and Xiao J: MiR-126-5p regulates osteoclast differentiation and bone resorption in giant cell tumor through inhibition of MMP-13. Biochem Biophys Res Commun. 443:944–949. 2014. View Article : Google Scholar : PubMed/NCBI
22	El-Kenawi AE and El-Remessy AB: Angiogenesis inhibitors in cancer therapy: Mechanistic perspective on classification and treatment rationales. Br J Pharmacol. 170:712–729. 2013. View Article : Google Scholar : PubMed/NCBI
23	Liu B, Peng XC, Zheng XL, Wang J and Qin YW: MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. 66:169–175. 2009. View Article : Google Scholar : PubMed/NCBI
24	Zhu X, Li H, Long L, Hui L, Chen H, Wang X, Shen H and Xu W: miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin (Shanghai). 44:519–526. 2012. View Article : Google Scholar : PubMed/NCBI
25	Zhu N, Zhang D, Xie H, Zhou Z, Chen H, Hu T, Bai Y, Shen Y, Yuan W, Jing Q and Qin Y: Endothelial-specific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2. Mol Cell Biochem. 351:157–164. 2011. View Article : Google Scholar : PubMed/NCBI
26	Feng R, Chen X, Yu Y, Su L, Yu B, Li J, Cai Q, Yan M, Liu B and Zhu Z: miR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett. 298:50–63. 2010. View Article : Google Scholar : PubMed/NCBI