| Title | Pulmonary cell-type specific modifications of matrix metalloproteinases induced by hypoxia and/or platelet-derived growth factor-BB | |
| Authors | G. Karakiulakis¹, E. Papakonstantinou¹, A.J. Aletras², M. Tamm³ and M. Roth³
1. Dept Pharmacology, School of Medicine, Aristotle Univ., 54124 Thessaloniki, Greece 2. Lab Biochemistry, Dept Chemistry, Univ. of Patras, 26110, Greece 3. Pulmonary Cell Research and Pneumology, Univ. Hospital Basel, 4031, Switzerland |
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| Citation | Karakiulakis, G., Papakonstantinou, E., Aletras, A.J., Tamm, M., Roth, M.: Pulmonary cell-type specific modifications of matrix metalloproteinases induced by hypoxia and/or platelet-derived growth factor-BB, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 195-197 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Hypoxia, platelet-derived growth factor-BB, lung fibroblasts, pulmonary vascular smooth muscle cells, MMP, TIMP. | |
| Other Terms | review article | |
| Summary | Hypoxia, a common manifestation in various lung pathologies, is linked to extensive remodeling of the extracellular matrix in the affected tissue, and involves, among others, disrupted homeostasis of collagenous proteins. In this study we demonstrated that hypoxia up- regulated the expression of matrix metalloproteinase (MMP)-1 in human pulmonary vascular smooth muscle cells (VSMC) and human lung fibroblasts (LF) and MMP- 13 in LF only. The hypoxia induced upregulation of MMP was inhibited by platelet-derived growth factor-BB (PDGF- BB). The expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 was not affected by hypoxia, but TIMP-1 was significantly elevated by PDGF in both cell types. Hypoxia in combination with PDGF stimulated the production of soluble collagen type I by LF. Our data suggest that the combination of hypoxia and PDGF has a synergistic net-effect leading to accumulation of collagenous protein that may be associated to lung pathology. | |
| References | 1. Joon Yun A., Lee P.Y., Bazar K.A.: Autonomic dysregulation as a basis of cardiovascular, endocrine, and inflammatory disturbances associated with obstructive sleep apnea and other conditions of chronic hypoxia, hypercapnia, and acidosis. Med. Hypotheses 62: 852-856 (2004)
2. Tamm M., Bihl M., Eickelberg 0., Stulz P., Perruchoud A.P., Roth M.: Hypoxia-induced interleukin-6 and interleukin-8 production is mediated by platelet-activating factor and platelet-derived growth factor in primary human lung cells. Am. J. Respir. Cell Mol. Biol. 19: 653-661 (1998) 3. Papakonstantinou E., Karakiulakis G., Roth M., Block L.H.: Platelet-derived growth factor stimulates the secretion of hyaluronic acid by proliferating human vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA 92: 9881-9885 (1995) 4. Papakonstantinou E., Karakiulakis G., Eickelberg 0., Perruchoud A.P., Block L.H., Roth M.: A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration. Glycobiology 8: 821-830 (1998) 5. Papakonstantinou E., Roth M., Block L.H., Mirtsou-Fidani V., Argiriadis P., Karakiulakis G.: The differential distribution of hyaluronic acid in the layers of human atheromatic aortas is associated with vascular smooth muscle cell proliferation and migration. Atherosclerosis 138: 79-89 (1998) 6. Papakonstantinou E., Karakiulakis G., Tamm M., Perruchoud A.P., Roth M.: Hypoxia modifies the effect of PDGF on glycosaminoglycan synthesis by primary human lung cells. Am. J. Physiol. Lung Cell Mol. Physiol. 279: L825-L834 (2000) 7. Papakonstantinou E., Aletras A.J., Roth M., Tamm M., Karakiulakis G.: Hypoxia modulates the effects of transforming growth factor-beta isoforms on matrix-formation by primary human lung fibroblasts. Cytokine 24: 25-35 (2003) 8. Zijlstra A., Aimes R.T., Zhu D., et al.: Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase- 13 (collagenase-3). J. Biol. Chem. 279: 27633-27645 (2004) 9. Fathke C., Wilson L., Hutter J., et al.: Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 22: 812-822 (2004) 10. Roth M., Nauck M., Yousefi S., et al.: Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin-6 and interleukin-8 in human lung fibroblasts via binding to its functional receptor. J. Exp. Med. 184: 191-201 (1996) 11. Papakonstantinou E., Roth M., Tamm M., Eickelberg O., Perruchoud A.P., Karakiulakis G.: Hypoxia differentially enhances the effects of transforming growth factor-b isoforms on the synthesis and secretion of glycosaminoglycans by human lung fibroblasts. J. Pharmacol. Exp. Ther. 301: 830-837 (2002) 12. Syggelos S.A., Eleftheriou S.C., Giannopoulou E., Pana- giotopoulos E., Aletras A.J.: Gelatinolytic and collagenolytic activity in periprosthetic tissues from loose hip endoprostheses. J. Rheumatol. 28: 1319-1329 (2001) 13. Abraham L.C., Vorrasi J., Kaplan D.L.: Impact of collagen structure on matrix trafficking by human fibroblasts. J. Biomed. Mater Res. 70A: 39-48 (2004) |
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Online ISSN 1011-6575
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