Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO.
Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. The abnormal MSCs in proliferation and function were reported at maternal fetal interface in patients with pre-eclampsia (PE). Long non-coding RNA MALAT1 was known to regulate the function of trophoblast cells. However, it is not clear whether MALAT1 regulates MSCs to be related to PE. In the present study, we found that the expression of MALAT1 was significantly reduced in both umbilical cord tissues and MSCs in patients with severe PE. MALAT1 did not affect the phenotype and differentiation of MSCs. Of note, transfection with MALAT1 plasmid into MSCs drove the cell cycle into G2/M phase and inhibited cell apoptosis. The supernatants from MALAT1-overexpressed MSCs promoted the migration of MSCs, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-MALAT1 had the opposite effects. Moreover, we found that MALAT1-induced VEGF mediated these effects of MALAT1 on MSCs. Furthermore, we found that MALAT1-overexpressed MSCs promoted M2 macrophage polarization and this effect was mediated by MALAT1-induced IDO expression, suggesting that MALAT1 may enhance the immunosuppressive properties of MSCs in vivo. In addition, we also investigated the factors that inhibit MALAT1 expression in PE and found that peroxide was a cause for MALAT1 downregulation. Taken together, our data demonstrate that MALAT1 is an important endogenous regulator in the proliferation, angiogenesis, and immunosuppressive properties of MSCs, suggesting it may be involved in the pathogenesis of PE. J. Cell. Biochem. 118: 2780-2791, 2017. © 2017 Wiley Periodicals, Inc.
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Xiujun
X
Li
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Yuxian
Y
Song
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Fei
F
Liu
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Dan
D
Liu
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Huishuang
H
Miao
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Jing
J
Ren
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Jingjing
J
Xu
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Liang
L
Ding
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
Yali
Y
Hu
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Zhiqun
Z
Wang
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Yayi
Y
Hou
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Guangfeng
G
Zhao
D049109:Cell Proliferation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D018919:Neovascularization, Physiologic / Q000276:immunology*; D011225:Pre-Eclampsia / Q000276:immunology; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
3-DIOXYGENASE; INDOLEAMINE 2; MESENCHYMAL STEM CELLS; METASTASIS-ASSOCIATED LUNG ADENOCARCINOMA TRANSCRIPT 1; VASCULAR ENDOTHELIAL GROWTH FACTOR