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

  • Lim, Yoonhwa (Dept. of Biotechnology, Seoul Women's University) ;
  • Lee, Minji (Dept. of Biotechnology, Seoul Women's University) ;
  • Jeong, Hyeju (Dept. of Biotechnology, Seoul Women's University) ;
  • Kim, Haekwon (Dept. of Biotechnology, Seoul Women's University)
  • 투고 : 2017.04.28
  • 심사 : 2017.05.11
  • 발행 : 2017.06.30

초록

Human adult stem cells have widely been examined for their clinical application including their wound healing 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.

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참고문헌

  1. Andrae J, Gallini R, Betsholtz C. (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276-1312. https://doi.org/10.1101/gad.1653708
  2. Beltrami AP, Cesselli D, Bergamin N, Marcon P, Rigo S, Puppato E, D'Aurizio F, Verardo R, Piazza S, Pignatelli A, Poz A, Baccarani U, Damiani D, Fanin R, Mariuzzi L, Finato N, Masolini P, Burelli S, Belluzzi O, Schneider C, Beltrami CA (2006) Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood 110:3438-3446.
  3. Chen Q, Jin M, Yang F, Zhu J, Xiao Q, Zhang L (2013) Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm 2013:e928315.
  4. De Becker A, Van Hummelen P, Bakkus M, Vande Broek I, De Wever J, De Waele M, Van Riet I (2007) Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 92:440-449. https://doi.org/10.3324/haematol.10475
  5. Ding J, Huang F, Wu G, Han T, Xu F, Weng D, Wu C, Zhang X, Yao Y, Zhu X (2015) MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. PLoS One 10:e0120321. https://doi.org/10.1371/journal.pone.0120321
  6. Endo H, Utani A, Shinkai H (2003) Activation of p38 MAPK suppresses matrix metalloproteinase-1 gene expression induced by platelet-derived growth factor. Arch Dermatol Res 294:552-558. https://doi.org/10.1007/s00403-002-0364-5
  7. Fan HX, Chen Y, Ni BX, Wang S, Sun M, Chen D, Zheng JH (2015) Expression of MMP-1/PAR-1 and patterns of invasion in oral squamous cell carcinoma as potential prognostic markers. Onco Targets Ther 3:1619-1626.
  8. Galderisi U, Giordano A (2014) The gap between the physiological and therapeutic roles of mesenchymal stem cells. Med Res Rev 34:1100-1126. https://doi.org/10.1002/med.21322
  9. Gao H, Priebe W, Glod J, Banerjee, D. (2009) Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells 27:857-865. https://doi.org/10.1002/stem.23
  10. Gehmert S, Gehmert S, Prantl L, Vykoukal J, Alt E, Song YH (2010) Breast cancer cells attract the migration of adipose tissue-derived stem cells via the PDGF-BB/ PDGFR-beta signaling pathway. Biochem Biophys Res Commun 398:601-605. https://doi.org/10.1016/j.bbrc.2010.06.132
  11. Gentilini D, Busacca M, Di Francesco S, Vignali M, Vigano P, Di Blasio AM (2007) PI3K/Akt and ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17beta-estradiol and growth factors. Mol Hum Reprod 13:317-322. https://doi.org/10.1093/molehr/gam001
  12. Gentilini D, Busacca M, Di Francesco S, Vignali M, Vigano P, Di Blasio AM (2007) PI3K/Akt and ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17beta-estradiol and growth factors. Mol Hum Reprod 13:317-322. https://doi.org/10.1093/molehr/gam001
  13. Harada T, Yamasaki A, Chikumi H, Hashimoto K, Okazaki R, Takata M, Fukushima T, Watanabe M, Kurai J, Halayko AJ, Shimizu E (2015) $\gamma$-Tocotrienol reduces human airway smooth muscle cell proliferation and migration. Pulm Pharmacol Ther 32:45-52. https://doi.org/10.1016/j.pupt.2015.04.003
  14. Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047-3055.
  15. Hirayama K, Hata Y, Noda Y, Miura M, Yamanaka I, Shimokawa H, Ishibashi T (2004) The involvement of the rho-kinasepathway and its regulation in cytokineinduced collagen gel contraction by hyalocytes. Invest Ophthalmol Vis Sci 45:3896-3903. https://doi.org/10.1167/iovs.03-1330
  16. Ho IA, Yulyana Y, Sia KC, Newman JP, Guo CM, Hui KM, Lam PY (2014) 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. FASEB J 28:4359-4368. https://doi.org/10.1096/fj.14-252551
  17. Kim JH, Park SG, Kim W-K, Song SU, Sung J-H (2015) Functional regulation of adipose-derived stem cells by PDGF-D. Stem Cells 33:542-556. https://doi.org/10.1002/stem.1865
  18. Ito I, Fixman ED, Asai K, Yoshida M, Gounni AS, Martin JG, Hamid Q (2009) Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix metalloproteinases and migratory function of human airway smooth muscle cells. Clin Exp Allergy 39:1370-1380. https://doi.org/10.1111/j.1365-2222.2009.03293.x
  19. Karp JM, Leng Teo GS (2009) Mesenchymal stem cell homing: The devil is in the details. Cell Stem Cell 4: 206-216. https://doi.org/10.1016/j.stem.2009.02.001
  20. Kavanagh DP, Suresh S, Newsome PN, Frampton J, Kalia N (2015) Pretreatment of mesenchymal stem cells manipulates their vasculoprotective potential while not altering their homing within the injured gut. Stem Cells 33:2785-2797. https://doi.org/10.1002/stem.2061
  21. Kim JH, Park SG, Song SY, Kim JK, Sung JH (2013) Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2. Cell Death Dis 4:e588. https://doi.org/10.1038/cddis.2013.117
  22. Kim SJ, Shin JY, Lee KD, Bae YK, Choi IJ, Park SH, Chun KH (2011) Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP- 1). PLoS One 6:e25103. https://doi.org/10.1371/journal.pone.0025103
  23. Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M (2005) Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 308:1472-1477. https://doi.org/10.1126/science.1107627
  24. Kumar JD, Steele I, Moore AR, Murugesan SV, Rakonczay Z, Venglovecz V, Pritchard DM, Dimaline R, Tiszlavicz L, Varro A, Dockray GJ (2015) Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 309:G78-86. https://doi.org/10.1152/ajpgi.00084.2015
  25. Li X, Bai J, Ji X, Li R, Xuan Y, Wang Y (2014) Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation. Int J Mol Med 34:695-704. https://doi.org/10.3892/ijmm.2014.1821
  26. Liao HT, Chen CT (2014) Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells. World J Stem Cells 6:288-295. https://doi.org/10.4252/wjsc.v6.i3.288
  27. Lopatina T, Bruno S, Tetta C, Kalinina N, Porta M, Camussi G (2014) Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun Signal 10:e1186.
  28. Maijenburg MW, Noort WA, Kleijer M, Kompier CJ, Weijer K, van Buul JD, van der Schoot CE, Voermans C (2009) Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesenchymal stromal cells. Br J Haematol 148:428-440.
  29. Montanari S, Dayan V, Yannarelli G, Billia F, Viswanathan S, Connelly KA, Keating A (2015) Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model. J Heart Lung Transplant 34:1481-1488. https://doi.org/10.1016/j.healun.2015.05.008
  30. Nabai L, Kilani RT, Aminuddin F, Li Y, Ghahary A (2015) Methotrexate modulates the expression of MMP-1 and type 1 collagen in dermal fibroblast. Mol Cell Biochem 409:213-224. https://doi.org/10.1007/s11010-015-2526-8
  31. Nagineni CN, Kutty V, Detrick B, Hooks JJ (2005) Expression of PDGF and their receptors in human retinal pigment epithelial cells and fibroblasts: Regulation by TGF-beta. J Cell Physiol 203:35-43. https://doi.org/10.1002/jcp.20213
  32. Nhung TH, Nam NH, Nguyen NT, Nghia H, Van Thanh N, Ngoc PK, Van Pham P (2015) A comparison of the chemical and liver extract-induced hepatic differentia-tion of adipose derived stem cells. In Vitro Cell Dev Biol Anim 51:1085-1092. https://doi.org/10.1007/s11626-015-9939-2
  33. Ould-Yahoui A, Sbai O, Baranger K, Bernard A, Gueye Y, Charrat E, Clement B, Gigmes D, Dive V, Girard SD, Feron F, Khrestchatisky M, Rivera S (2013) Role of matrix metalloproteinases in migration and neurotrophic properties of nasal olfactory stem and ensheathing cells. Cell Transplant 22:993-1010. https://doi.org/10.3727/096368912X657468
  34. Ozaki Y, Nishimura M, Sekiya K, Suehiro F, Kanawa M, Nikawa H, Hamada T, Kato Y (2006) Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev 16:119-129.
  35. Perico N, Casiraghi F, Gotti E, Introna M, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Noris M, Remuzzi G (2013) Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation. Transpl Int 26:867-878. https://doi.org/10.1111/tri.12132
  36. Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, Charbord P, Domenech J (2007) The in vitro migration capacity of human bone marrow me-senchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25: 1737-1745. https://doi.org/10.1634/stemcells.2007-0054
  37. Ponte AL, Ribeiro-Fleury T, Chabot V, Gouilleux F, Lan-gonne A, Herault O, Charbord P, Domenech J (2012) Granulocyte-colony-stimulating factor stimulation of bone marrow mesenchymal stromal cells promotes CD34+ cell migration via a matrix metalloproteinase-2-dependent mechanism. Stem Cells Dev 21:3162-3172. https://doi.org/10.1089/scd.2012.0048
  38. Potapova IA, Gaudette GR, Brink PR, Robinson RB, Rosen MR, Cohen IS, Doronin SV (2007) Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro. Stem Cells 25:1761-1768. https://doi.org/10.1634/stemcells.2007-0022
  39. Raffetto JD, Khalil RA (2007) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346-359.
  40. Rhee S, Ho CH, Grinnell F (2009) Promigratory and procontractile growth factor environments differentially regulate cell morphogenesis. Exp Cell Res 316:232-244.
  41. Rossello A, Nuti E, Orlandini E, Carelli P, Rapposelli S, Macchia M, Minutolo F, Carbonaro L, Albini A, Benelli R, Cercignani G, Murphy G, Balsamo A (2004) New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2). Bioorg Med Chem 12:2441-2450. https://doi.org/10.1016/j.bmc.2004.01.047
  42. Ryu YJ, Cho TJ, Lee DS, Choi JY, Cho J (2013) Phenotypic characterization and in vivo localization of human adipose-derived mesenchymal stem cells. Mol Cells 35:557-564. https://doi.org/10.1007/s10059-013-0112-z
  43. Shi M, Li J, Liao L, Chen B, Li B, Chen L, Jia H, Zhao RC (2007) Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica 92:897-904. https://doi.org/10.3324/haematol.10669
  44. Veevers-Lowe J, Ball SG, Shuttleworth A, Kielty CM (2011) Mesenchymal stem cell migration is regulated by fibronectin through ${\alpha}5{\beta}1$-integrin-mediated activation of PDGFR-${\beta}$ and potentiation of growth factor signals. J Cell Sci 124:1288-1300. https://doi.org/10.1242/jcs.076935
  45. Veevers-Lowe J, Ball SG, Shuttleworth A, Kielty CM (2011) Mesenchymal stem cell migration is regulated by fibronectin through ${\alpha}5{\beta}1$-integrin-mediated activation of PDGFR-${\beta}$ and potentiation of growth factor sig-nals. J Cell Sci 124:1288-1300. https://doi.org/10.1242/jcs.076935
  46. Wang W, Pan H, Murray K, Jefferson BS, Li Y (2009) Ma-trix metalloproteinase-1 promotes muscle cell migration and differentiation. Am J Pathol 174:541-549. https://doi.org/10.2353/ajpath.2009.080509
  47. Xia P, Zhang R, Ge G (2015) C/$EBP{\beta}$ mediates TNF-${\alpha}$-induced cancer cell migration by inducing MMP expression dependent on p38 MAPK. J Cell Biochem 116: 2766-2777. https://doi.org/10.1002/jcb.25219
  48. Zhou YM, Lan X, Guo HB, Zhang Y, Ma L, Cao JB (2014) Rho/ROCK signal cascade mediates asymmetric dime-thylarginine-induced vascular smooth muscle cells migration and phenotype change. Biomed Res Int 2014: e83707.