Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death

사멸세포에서의 metalloproteinase-9의 작용

  • Lee, Kyeong-Ah (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Kim, Sun-Mi (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Kim, Koan-Hoi (Department of Pharmacology, School of Medicine, Pusan National University)
  • 이경아 (부산대학교 의학전문대학원 약리학교실) ;
  • 김선미 (부산대학교 의학전문대학원 약리학교실) ;
  • 김관회 (부산대학교 의학전문대학원 약리학교실)
  • Published : 2006.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study investigated whether matrix metalloproteinases (MMPs) can be modified in apoptotic smooth muscle cell (SMC) using the SMC that undergoes apoptotic death by expressing Fas-associated death domain containing protein (FADD) when they are grown without tetracycline in culture medium. In the absence of tetracycline, FADD-SMC lost adherence and showed the fragmentation of the nuclei. In proportion to duration of tetracycline removal, phosphorylated form of p38 MAPK and of ERK increased, whereas phosphorylation of protein kinase B (PKB) was not changed very much in response to tetracycline The levels of cyclin A and cyclin D were also decreased in a time dependent manner. Up-regulation of MMP-9 expression and activity was observed when the SMC were grown without tetracycline. Immunoreactivity of MMP-9 was detected from both attached and floating FADD-SMCs grown without tetracycline. An inhibitor of MAPK kinase, PD098059, and an inhibitor of p38 MAPK, SB203580, inhibited the up-regulation of MMP-9. Treatment of the SMC with a synthetic MMP inhibitor, BB94, attenuated death occurring in the absence of tetracycline. These results indicate that SMC undergoing death is able to up-regulate MMP-9 and that the enzyme can affect cell viability.

배지에 tetracycline이 없으면 사멸하는 평활근세포 (FADD-SMC)를 이용하여 metalloproteinase (MMP)와 사멸세포의 상관관계를 조사하였다. FADD-SMC를 tetracycline이 없는 배지에서 배양하는 경우 핵이 조각으로 잘라졌고 인산화한 p38과 ERK가 증가하고 MMP-9의 발현과 활성이 증가한 반면, cyclin D와 cyclin D의 발현은 감소하였다. 그리고 죽는 FADD-SMC에서 MMP-9의 발현은 immunofluorescen로 재확인하였다. MMP-9의 증가는 MAPK 억제제인 PD098059와 p38 MAPK 억제제인 SB203S80에 의하여 감소하였다. 그리고 MMP 억제제인 BB94는 FADD-SMC의 사멸을 감소시켰다.

Keywords

References

  1. Alexander CM, EW. Howard, MJ. Bissell, Z. Werb. 1996. Rescue of mammary epithelial cell apoptosis and entactin degradation by a tissue inhibitor of metalloproteinases-1 transgene. J. Cell Biol. 135, 1669-77 https://doi.org/10.1083/jcb.135.6.1669
  2. Bauriedel G, R Hutter, U Welsch, R Bach, H Sievert, B Luderitz. 1999. Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability. Cardiovasc. Res. 41, 480-8 https://doi.org/10.1016/S0008-6363(98)00318-6
  3. Boudreau N, CJ Sympson, Z Werb, MJ Bissell. 1995. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267, 891-3 https://doi.org/10.1126/science.7531366
  4. Chakraborti S, M Marldal, S Das, A Mandal, T Chakraborti. 2003. Regulation of matrix metalloproteinases: an overview. Mol. Cell. Biochem. 253, 269-85 https://doi.org/10.1023/A:1026028303196
  5. Chintala SK, X Zhang, JS Austin, ME Fini. 2002. Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation. J. BioI. Chem. 277, 47461-8 https://doi.org/10.1074/jbc.M204824200
  6. Cho A, J Graves, MA Reidy. 2000. Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 20, 2527-32 https://doi.org/10.1161/01.ATV.20.12.2527
  7. Galis ZS, JJ Khatri. 2002. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ. Res. 90, 251-62
  8. Galis ZS, M Muszynski, GK Sukhova, E Simon-Morrissey, P Libby. 1995. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann. N. Y. Acad. Sci. 748, 501-7
  9. Galis ZS, GK Sukhova, MW Lark, P Libby. 1994. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin. Invest. 94, 2493-503 https://doi.org/10.1172/JCI117619
  10. Gum R, H Wang, E Lengyel, J Juarez, D Boyd. 1997. Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades. Oncogene 14, 1481-93 https://doi.org/10.1038/sj.onc.1200973
  11. Knox JB, GK Sukhova, AD Whittemore, P Libby. 1997. Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Circulation 95, 205-12 https://doi.org/10.1161/01.CIR.95.1.205
  12. Kockx MM, AG Herman. 2000. Apoptosis in atherosclerosis:beneficial or detrimental? Cardiovasc. Res. 45, 736-46 https://doi.org/10.1016/S0008-6363(99)00235-7
  13. Libby P, M Aikawa. 2002. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat. Med. 8, 1257-62 https://doi.org/10.1038/nm1102-1257
  14. Loftus IM, S Goodall, M Crowther, L Jones, PR Bell, AR Naylor, 1999. Thompson MM. Increased MMP-9 activity in acute carotid plaques: therapeutic avenues to prevent stroke. Ann. N. Y. Acad. Sci. 878, 551-4 https://doi.org/10.1111/j.1749-6632.1999.tb07724.x
  15. Mandal M, A Mandal, S Das, T Chakraborti, c Sajal. 2003. Clinical implications of matrix metalloproteinases. Mol. Cell. Biochem. 252, 305-29 https://doi.org/10.1023/A:1025526424637
  16. McCawley LJ, LM Matrisian. 2001. Matrix metalloproteinases:they're not just for matrix anymore! Curr. Opin. Cell Biol. 13, 534-40 https://doi.org/10.1016/S0955-0674(00)00248-9
  17. Mott JD, Z Werb. 2004. Regulation of matrix biology by matrix metalloproteinases. Curr. Opin. Cell. Biol. 16, 558-64 https://doi.org/10.1016/j.ceb.2004.07.010
  18. Nguyen M, J Arkell, CJ Jackson. 1998. Active and tissue inhibitor of matrix metalloproteinase-free gelatinase B accumulates within human microvascular endothelial vesicles. J. Biol. Chem. 273, 5400-4 https://doi.org/10.1074/jbc.273.9.5400
  19. Ram M, Y Sherer, Y Shoenfeld. 2006. Matrix metalloproteinase-9 and autoimmune diseases. J. Clin. Immunol. 26, 299-307 https://doi.org/10.1007/s10875-006-9022-6
  20. Schonbeck U, F Mach, GK Sukhova, C Murphy, JY Bonnefoy, RP Fabunmi, P Libby. 1997. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes:a role for CD40 signaling in plaque rupture? Circ. Res. 81, 448-54 https://doi.org/10.1161/01.RES.81.3.448
  21. Simon C, H Goepfert, D Boyd. 1998. Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res. 58, 1135-9
  22. Simon C, MJ Hicks, AJ Nemechek, R Mehta, Jr. O'MalleyBW, H Goepfert, CM Flaitz, D Boyd. 1999. PD 098059, an inhibitor of ERK1 activation, attenuates the in vivo invasiveness of head and neck squamous cell carcinoma. Br. J. Cancer 80, 1412-9 https://doi.org/10.1038/sj.bjc.6690537
  23. Sinha S, WH Frishman. 1998. Matrix metalloproteinases and abdominal aortic aneurysms: a potential therapeutic target. J. Clin. Pharmacol. 38, 1077-88
  24. Sukhova GK, U Schonbeck., E Rabkin, FJ Schoen, AR Poole, RC Billinghurst, P Libby. 1999. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 99, 2503-9 https://doi.org/10.1161/01.CIR.99.19.2503
  25. Vaillant C, C Meissirel, M Mutin, MF Belin, LR Lund, N Thomasset. 2003. MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum. Mol. Cell. Neurosci. 24, 395-408 https://doi.org/10.1016/S1044-7431(03)00196-9