Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are critical regulators in organ development. Among them, miR-191 is known to be regulated in early embryogenesis and dysregulated in cancer. This role in undifferentiated tissues suggests a possible part of miR-191 also in bone marrow derived mesenchymal stem cells (BMSCs) physiology. Here, we report that miR-191 decreased MMP expression and migration of BMSCs. Conditioned media of miR-191 overexpressing BMSCs block VEGF expression, and inhibit angiogenesis of HUVECs. Under osteogenic culture conditions, inhibition of miR-191 significantly induces bone formation. Moreover, our studies showed miR-191 might influence chondrogenesis of BMSCs by directly targeting CCAAT Enhancer Binding Protein Beta (CEBPB). Taken together, here we demonstrate the role of miR-191 in differentiation, migration and paracrine function of BMSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Almeida MI, Silva AM, Vasconcelos DM, Almeida CR et al (2016) miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis. Oncotarget 7:7–22

    Article  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Bianco P, Cao X, Frenette PS, Mao JJ et al (2013) The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nature medicine 19:35–42

    Article  CAS  Google Scholar 

  • Brodie S, Lee HK, Jiang W, Cazacu S et al (2017) The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells. Oncotarget 8:31785–31801

    Article  Google Scholar 

  • Chen S, Xu Z, Shao J, Fu P, Wu H (2019) MicroRNA-218 promotes early chondrogenesis of mesenchymal stem cells and inhibits later chondrocyte maturation. BMC Biotechnol 19:6

    Article  Google Scholar 

  • Collino F, Bruno S, Deregibus MC, Tetta C, Camussi G (2011) MicroRNAs and mesenchymal stem cells. Vitamins hormones 87:291–320

    Article  CAS  Google Scholar 

  • Copland IB, Lord-Dufour S, Cuerquis J, Coutu DL et al (2009) Improved autograft survival of mesenchymal stromal cells by plasminogen activator inhibitor 1 inhibition. Stem Cells 27:467–477

    Article  CAS  Google Scholar 

  • Cui X, Breitenkamp K, Finn MG, Lotz M et al (2012a) Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng Part A 18:1304–1312

    Article  CAS  Google Scholar 

  • Cui X, Breitenkamp K, Lotz M, D’Lima D (2012b) Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation. Biotechnol Bioeng 109:2357–2368

    Article  CAS  Google Scholar 

  • Dangwal S, Stratmann B, Bang C, Lorenzen JM et al (2015) Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines. Arterioscler Thromb Vasc Biol 35:1480–1488

    Article  CAS  Google Scholar 

  • De Boeck A, Pauwels P, Hensen K, Rummens JL et al (2013) Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut 62:550–560

    Article  Google Scholar 

  • Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM et al (2011) MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci USA 108:6139–6144

    Article  Google Scholar 

  • Forte G, Minieri M, Cossa P, Antenucci D et al (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33

    Article  CAS  Google Scholar 

  • Gao G, Schilling A, Yonezawa T, Wang J, Dai G, Cui X (2014) Bioactive Nanoparticles Stimulate Bone Tissue Formation in Bioprinted Three-Dimensional Scaffold and Human Mesenchymal Stem Cells. Biotechnol J 9(10):1304–1311

    Article  CAS  Google Scholar 

  • Gao G, Schilling A, Hubbell K, Yonezawa T, Truong D, Hong Y, Dai G, Cui X (2015a) Improved Properties of Bone and Cartilage Tissue from 3D Inkjet-bioprinted Human Mesenchymal Stem Cells by Simultaneous Deposition and Photocrosslinking in PEG-GelMA. Biotech Lett 37(11):2349–2355

    Article  CAS  Google Scholar 

  • Gao G, Yonezawa T, Hubbell K, Dai G, Cui X (2015b) Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. Biotechnol J 10(10):1568–1577

    Article  CAS  Google Scholar 

  • Gao G, Zhang X, Hubbell K, Cui X (2017) NR2F2 Regulates Chondrogenesis of Human Mesenchymal Stem Cells in Bioprinted Cartilage. Biotechnol Bioeng 114(1):208–216

    Article  CAS  Google Scholar 

  • Guan X, Gao Y, Zhou J, Wang J et al (2015) miR-223 Regulates Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells Through a C/EBPs/miR-223/FGFR2 Regulatory Feedback Loop. Stem Cells 33:1589–1600

    Article  CAS  Google Scholar 

  • Guerzoni C, Bardini M, Mariani SA, Ferrari-Amorotti G et al (2006) Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. Blood 107:4080–4089

    Article  CAS  Google Scholar 

  • Hadjimichael C, Nikolaou C, Papamatheakis J, Kretsovali A (2016) MicroRNAs for Fine-Tuning of Mouse Embryonic Stem Cell Fate Decision through Regulation of TGF-beta Signaling. Stem cell reports 6:292–301

    Article  CAS  Google Scholar 

  • Kiezun A, Artzi S, Modai S, Volk N et al (2012) miRviewer: a multispecies microRNA homologous viewer. BMC Res Notes 5:92

    Article  CAS  Google Scholar 

  • Kusuma GD, Carthew J, Lim R, Frith JE (2017) Effect of the Microenvironment on Mesenchymal Stem Cell Paracrine Signaling: Opportunities to Engineer the Therapeutic Effect. Stem Cells Dev 26:617–631

    Article  CAS  Google Scholar 

  • Li H, Li T, Fan J, Li T et al (2015) miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway. Cell death differentiation 22:1935–1945

    Article  CAS  Google Scholar 

  • Liu L, Liu H, Chen M, Ren S et al (2017) miR-301b ~ miR-130b-PPARgamma axis underlies the adipogenic capacity of mesenchymal stem cells with different tissue origins. Scientific reports 7:1160

    Article  Google Scholar 

  • Nagpal N, Kulshreshtha R (2014) miR-191: an emerging player in disease biology. Frontiers in genetics 5:99

    Article  Google Scholar 

  • Neuss S, Becher E, Woltje M, Tietze L, Jahnen-Dechent W (2004) Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells 22:405–414

    Article  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  Google Scholar 

  • Ries C, Egea V, Karow M, Kolb H et al (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109:4055–4063

    Article  CAS  Google Scholar 

  • Skarn M, Namlos HM, Noordhuis P, Wang MY et al (2012) Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222. Stem Cells Dev 21:873–883

    Article  CAS  Google Scholar 

  • TIAN J, RUI Y-J, Y.-J.XU, S.-A.ZHANG (2018) MiR-143-3p regulates early cartilage differentiation of BMSCs and promotes cartilage damage repair through targeting BMPR2. Eur Rev Med Pharmacol Sci 22:8814–8821

    CAS  PubMed  Google Scholar 

  • Wang S, Qu X, Zhao RC (2012) Clinical applications of mesenchymal stem cells. J Hematol Oncol 5:19

    Article  Google Scholar 

  • Xia P, Zhang R, Ge G (2015) C/EBPbeta Mediates TNF-alpha-Induced Cancer Cell Migration by Inducing MMP Expression Dependent on p38 MAPK. Journal of cellular biochemistry 116:2766–2777

    Article  CAS  Google Scholar 

  • Xu W, Ji J, Xu Y, Liu Y et al (2015) MicroRNA-191, by promoting the EMT and increasing CSC-like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells. Molecular carcinogenesis 54(Suppl 1):E148–E161

    Article  CAS  Google Scholar 

  • Yang Z, Bian C, Zhou H, Huang S et al (2011) MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cells Dev 20:259–267

    Article  CAS  Google Scholar 

  • Zhang XF, Li KK, Gao L, Li SZ et al (2015) miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPbeta. Oncotarget 6:4144–4158

    Article  Google Scholar 

  • Zhang XF, Sun RQ, Jia YF, Chen Q et al (2016) Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents. Scientific reports 6:33204

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81970543, 81570591, and 31800847), State Commission of Science and Technology of Hubei China (ZRMS2018000319), Fundamental Research Funds for the Central Universities (WUT: 2015IB004, 2017IB004, 2017IVA112). The authors declare non-financial conflict of interest.

Supporting information

Fig. S1 Relative miR-191 expression of miR-191 mimic and inhibitor transfected MSCs

Author information

Authors and Affiliations

  1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China

    Yuanxing Liu & Xi Liu

  2. Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310003, Zhejiang Province, China

    Yuanxing Liu & Xi Liu

  3. School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, Hubei Province, China

    Pengxiang Ye, Xiafei Zhang, Guifang Gao & Xiaofeng Cui

  4. Clinic for Trauma Surgery, Orthopaedic Surgery and Plastic Surgery, University Medical Center Göttingen, Robert Koch Strasse 40, 37075, Göttingen, Germany

    Arndt F. Schilling

  5. Center for Therapeutic Innovation, Gene Research Center for Frontier Life Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-14 Sakamoto, Nagasaki, 852-8523- 0022, Japan

    Tomo Yonezawa

  6. Department of Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Guifang Gao

Authors
  1. Yuanxing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pengxiang Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiafei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arndt F. Schilling
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomo Yonezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guifang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaofeng Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Guifang Gao or Xiaofeng Cui.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file 1 (TIF 306.2 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Liu, X., Ye, P. et al. MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis. Biotechnol Lett 42, 1777–1788 (2020). https://doi.org/10.1007/s10529-020-02907-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-020-02907-z

Keywords

Search

Navigation