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Involvement of PI3K and MMP1 in PDGF-induced Migration of Human Adipose-derived Stem Cells

이민지|정혜주|임윤화|김해권
한국발생생물학회 (The Korea Society Of Developmental Biology)|2017.06|발생과 생식 (DEVELOPMENT & REPRODUCTION)|제21권 제2호|pp. 167-180

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키워드

MigrationPI3KPDGFAdipose-derived stem cellsMatrix metalloproteinase-1
주제분류생물학

초록

Human adult stem cells have widely been examined for their clinical application including their wound heal-ing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

Abstract

Human adult stem cells have widely been examined for their clinical application including their wound heal-ing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

참고문헌 (48)

  1. Andrae J, "Role of platelet-derived growth factors in physiology and medicine", Genes Dev, 22, pp.1276~1312 (2008)
  2. Beltrami AP, "Multipotent cells can be ge-nerated in vitro from several adult human organs (heart, liver, and bone marrow)", Blood, 110, pp.3438~3446 (2006)
  3. Chen Q, "Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling", Mediators Inflamm, 2013, pp.e928315~ (2013)
  4. De Becker A, "Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by ma-trix metalloproteinase-2 and tissue inhibitor of metal-loproteinase-3", Haematologica, 92, pp.440~449 (2007)
  5. Ding J, "MiR-519d-3p sup-presses invasion and migration of trophoblast cells via targeting MMP-2", PLoS One, 10, pp.e0120321~ (2015)
  6. Endo H, "Activation of p38 MAPK suppresses matrix metalloproteinase-1 gene ex-pression induced by platelet-derived growth factor", Arch Dermatol Res, 294, pp.552~558 (2003)
  7. Fan HX, "Expression of MMP-1", PAR-1 and patterns of invasion in oral squamous cell carcinoma as poten-tial prognostic markers, 2015, pp.3, 1619~1626
  8. Galderisi U, "The gap between the phy-siological and therapeutic roles of mesenchymal stem cells", Med Res Rev, 34, pp.1100~1126 (2014)
  9. Gao H, "Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived fac-tor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medi-um", Stem Cells, 27, pp.857~865 (2009)
  10. Gehmert S, "Breast cancer cells attract the migration of adipose tissue-derived stem cells via the PDGF-BB", PDGFR-beta signaling pathway, 2010, pp.398, 601~605
  11. Gentilini D, "PI3K", Akt and ERK1, Mol Hum Reprod, pp.2007, 13[DOI]
  12. Gentilini D, "PI3K", Akt and ERK1, Mol Hum Reprod, pp.2007, 13[DOI]
  13. Harada T, "γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration", Pulm Pharmacol Ther, 32, pp.45~52 (2015)
  14. Hellström M, "Role of PDGF-B and PDGFR-beta in re-cruitment of vascular smooth muscle cells and peri-cytes during embryonic blood vessel formation in the mouse", Development, 126, pp.3047~3055 (1999)
  15. Hirayama K, "The involvement of the rho-kinasepathway and its regulation in cytokine-induced collagen gel contraction by hyalocytes", Invest Ophthalmol Vis Sci, 45, pp.3896~3903 (2004)
  16. Ho IA, "Matrix metalloproteinase-1-mediated mesenchymal stem cell tumor tropism is dependent on crosstalk with stromal derived growth factor 1", C-X-C chemokine receptor 4 axis, 2014, pp.28, 4359~4368
  17. Kim JH, "Functional regulation of adipose-derived stem cells by PDGF-D", Stem Cells, 33, pp.542~556 (2015)
  18. Ito I, "Platelet-derived growth factor and transforming growth factor-beta modulate the expres-sion of matrix metalloproteinases and migratory func-tion of human airway smooth muscle cells", Clin Exp Allergy, 39, pp.1370~1380 (2009)
  19. Karp JM, "Mesenchymal stem cell homing: The devil is in the details", Cell Stem Cell, 4, pp.206~216 (2009)
  20. Kavanagh DP, "Pretreatment of mesenchymal stem cells ma-nipulates their vasculoprotective potential while not al-tering their homing within the injured gut", Stem Cells, 33, pp.2785~2797 (2015)
  21. Kim JH, "Re-active oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2", Cell Death Dis, 4, pp.e588~ (2013)
  22. Kim SJ, "Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated re-ceptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP- 1)", PLoS One, 6, pp.e25103~ (2011)
  23. Kratchmarova I, "Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation", Science, 308, pp.1472~1477 (2005)
  24. Kumar JD, "Gastrin sti-mulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration", Am J Physiol Gastrointest Liver Physiol, 309, pp.G78~G86 (2015)
  25. Li X, "Compre-hensive characterization of four different populations of human mesenchymal stem cells as regards their im-mune properties, proliferation and differentiation", Int J Mol Med, 34, pp.695~704 (2014)
  26. Liao HT, "Osteogenic potential: Compari-son between bone marrow and adipose-derived mesen-chymal stem cells", World J Stem Cells, 6, pp.288~295 (2014)
  27. Lopatina T, "Platelet-derived growth factor regu-lates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential", Cell Commun Signal, 10, pp.e1186~ (2014)
  28. Maijenburg MW, "Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesen-chymal stromal cells", Br J Haematol, 148, pp.428~440 (2009)
  29. Montanari S, "Mesenchymal stro-mal cells improve cardiac function and left ventricular remodeling in a heart transplantation model", J Heart Lung Transplant, 34, pp.1481~1488 (2015)
  30. Nabai L, "Methotrexate modulates the expression of MMP-1 and type 1 collagen in dermal fibroblast", Mol Cell Biochem, 409, pp.213~224 (2015)
  31. Nagineni CN, "Ex-pression of PDGF and their receptors in human retinal pigment epithelial cells and fibroblasts: Regulation by TGF-beta", J Cell Physiol, 203, pp.35~43 (2005)
  32. Nhung TH, "A comparison of the chemical and liver extract-induced hepatic differentia-tion of adipose derived stem cells", In Vitro Cell Dev Biol Anim, 51, pp.1085~1092 (2015)
  33. Ould-Yahoui A, "Role of matrix metalloproteinases in migration and neurotro-phic properties of nasal olfactory stem and ensheathing cells", Cell Transplant, 22, pp.993~1010 (2013)
  34. Ozaki Y, "Comprehensive analysis of chemotactic factors for bone marrow me-senchymal stem cells", Stem Cells Dev, 16, pp.119~129 (2006)
  35. Perico N, "Mesenchy-mal stromal cells and kidney transplantation: pretrans-plant infusion protects from graft dysfunction while fostering immunoregulation", Transpl Int, 26, pp.867~878 (2013)
  36. Ponte AL, "The in vitro migration capacity of human bone marrow me-senchy-mal stem cells: comparison of chemokine and growth factor chemotactic activities", Stem Cells, 25, pp.1737~1745 (2007)
  37. Ponte AL, "Granulocyte-colony-stimulating factor stimulation of bone marrow mesenchymal stromal cells promotes CD34+ cell migration via a matrix metalloproteinase-2-depen-dent mechanism", Stem Cells Dev, 21, pp.3162~3172 (2012)
  38. Potapova IA, "Mesenchy-mal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro", Stem Cells, 25, pp.1761~1768 (2007)
  39. Raffetto JD, "Matrix metalloproteinases and their inhibitors in vascular remodeling and vascu-lar disease", Biochem Pharmacol, 75, pp.346~359 (2007)
  40. Rhee S, "Promigratory and pro-contractile growth factor environments differentially re-gulate cell morphogenesis", Exp Cell Res, 316, pp.232~244 (2009)
  41. Rossello A, "New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)", Bioorg Med Chem, 12, pp.2441~2450 (2004)
  42. 류영준, "Phenotypic Characterization and ln Vivo Localization of Human Adipose-Derived Mesenchymal Stem Cells", Molecules and Cells, 35(6), pp.557~567 (2013), 한국분자세포생물학회[DOI]
  43. Shi M, "Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD", SCID mice, 2007, pp.92, 897~904
  44. Veevers-Lowe J, "Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activa-tion of PDGFR-β and potentiation of growth factor signals", J Cell Sci, 124, pp.1288~1300 (2011)
  45. Veevers-Lowe J, "Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activa-tion of PDGFR-βand potentiation of growth factor sig-nals", J Cell Sci, 124, pp.1288~1300 (2011)
  46. Wang W, "Ma-trix metalloproteinase-1 promotes muscle cell migra-tion and differentiation", Am J Pathol, 174, pp.541~549 (2009)
  47. Xia P, "C", EBPβ mediates TNF-α-induced cancer cell migration by inducing MMP ex-pression dependent on p38 MAPK, 2015, pp.116, 2766~2777
  48. Zhou YM, "Rho", ROCK signal cascade mediates asymmetric dime-thylarginine-induced vascular smooth muscle cells mi-gration and phenotype change, 2014, pp.2014, e83707~

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