HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 2, 908-915, January 12, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/2/908    most recent M602178200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karakiulakis, G. Articles by Roth, M. Search for Related Content PubMed PubMed Citation Articles by Karakiulakis, G. Articles by Roth, M. Social Bookmarking                      What's this?

Cell Type-specific Effect of Hypoxia and Platelet-derived Growth Factor-BB on Extracellular Matrix Turnover and Its Consequences for Lung Remodeling^*

George Karakiulakis, Eleni Papakonstantinou, Alexios J. Aletras, Michael Tamm^¶, and Michael Roth^¶||1

From the Department of Pharmacology, School of Medicine, Aristotle University, GR-54124 Thessaloniki, Greece, Laboratory of Biochemistry, Department of Chemistry, University of Patras, GR-26110 Patras, Greece, ^¶Pulmonary Cell Research and Pneumology, University Hospital Basel, CH-4031 Basel, Switzerland, and ^||The Woolcock Institute for Medical Research, Sydney NSW-2050, Australia

Hypoxia is associated with extracellular matrix remodeling in several inflammatory lung diseases, such as fibrosis, chronic obstructive pulmonary disease, and asthma. In a human cell culture model, we assessed whether extracellular matrix modification by hypoxia and platelet-derived growth factor (PDGF) involves the action of matrix metalloproteinases (MMPs) and thereby affects cell proliferation. Expression of MMP and its activity were assessed by zymography and enzyme-linked immunosorbent assay in human lung fibroblasts and pulmonary vascular smooth muscle cells (VSMCs), and synthesis of soluble collagen type I was assessed by enzyme-linked immunosorbent assay. In both cell types, hypoxia up-regulated the expression of MMP-1, -2, and -9 precursors without subsequent activation. MMP-13 was increased by hypoxia only in fibroblasts. PDGF-BB inhibited the synthesis and secretion of all hypoxia-dependent MMP via Erk1/2 mitogen-activated protein (MAP) kinase activation. Hypoxia and PDGF-BB induced synthesis of soluble collagen type I via Erk1/2 and p38 MAP kinase. Hypoxia-induced cell proliferation was blocked by antibodies to PDGF-BB or by inhibition of Erk1/2 but not by the inhibition of MMP or p38 MAP kinase in fibroblasts. In VSMCs, hypoxia-induced proliferation involved Erk1/2 and p38 MAP kinases and was further increased by fibroblast-conditioned medium or soluble collagen type I via Erk1/2. In conclusion, hypoxia controls tissue remodeling and proliferation in a cell type-specific manner. Furthermore, fibroblasts may affect proliferation of VSMC indirectly by inducing the synthesis of soluble collagen type I.

Received for publication, March 8, 2006 , and in revised form, September 11, 2006.

^* This work was supported by a grant from the Swiss National Fonds (SNF 32-061737). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Pulmonary Cell Research, Pneumology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Tel.: 41-61-2652391; Fax: 41-61-2652350; E-mail: Michaelr{at}med.usyd.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. J. Lee, K. H. In, J. H. Kim, S. Y. Lee, C. Shin, J. J. Shim, K. H. Kang, S. H. Yoo, C. H. Kim, H.-K. Kim, et al. Proteomic Analysis in Lung Tissue of Smokers and COPD Patients Chest, February 1, 2009; 135(2): 344 - 352. [Abstract] [Full Text] [PDF]

				W. J. French, E. E. Creemers, and M. D. Tallquist Platelet-Derived Growth Factor Receptors Direct Vascular Development Independent of Vascular Smooth Muscle Cell Function Mol. Cell. Biol., September 15, 2008; 28(18): 5646 - 5657. [Abstract] [Full Text] [PDF]

				S. Belmadani, M. Zerfaoui, H. A. Boulares, D. I. Palen, and K. Matrougui Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, {alpha}v{beta}3-integrin, and TGF-{beta}1 in response to ANG II and high glucose Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H69 - H76. [Abstract] [Full Text] [PDF]