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Matrix Metalloproteinase-9 Affects Three-Dimensional Collagen Gel Contraction

Pulmonary, Critical Care, and Sleep Medicine, University of Nebraska Medical Center, Omaha, Nebraska; and Washington University School of Medicine, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Tetsu Kobayashi, M.D., Ph.D., Division of Pulmonary and Critical Care Medicine, The Third Department of Internal Medicine, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-City, Mie 514-8507, Japan. E-mail: kobayashitetsu{at}hotmail.com

Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme implicated in many biological processes, including inflammation. It is produced by many cells, including fibroblasts. When cultured in three-dimensional (3D) collagen gels, fibroblasts can contract the surrounding matrix, a function that is believed to model the contraction that characterizes both normal wound repair and fibrosis. The current study was designed to evaluate the role of MMP-9 on fibroblast contraction of 3D collagen gels. Fibroblasts from mice lacking expression of MMP-9 and human lung fibroblasts (HFL-1) treated with or without MMP-9 small interference RNA (siRNA) were used. Fibroblasts were cast into type I collagen gels, floated in culture medium (Dulbecco's modified Eagle medium with 0.2% fetal calf serum) and cultured for 5 d. Gel size was determined daily using an image analysis system. Gels made from MMP-9 siRNA–treated human fibroblasts contracted less than control fibroblasts (66 vs. 88%; p < 0.05). Similarly, fibroblasts cultured from MMP-9–deficient mice contracted gels less than did fibroblasts from control mice (70 vs. 92%; p < 0.05), Transfection of the MMP-9–deficient murine fibroblasts with a vector expressing murine MMP-9 restored contractile activity to MMP-9–deficient fibroblasts (75 vs. 92%; p < 0.05). This study indicates that endogenous MMP-9 may regulate tissue contraction of 3D collagen gels mediated by fibroblasts.

FOOTNOTES

Conflict of Interest Statement: T.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. X.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Q.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.-Q.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.I.R. has participated as a speaker in scientific meetings and courses under the sponsorship of AstraZeneca and GlaxoSmithKline. He serves on advisory boards for Altana, AstraZeneca, Dey, GlaxoSmithKline, and Inspire. He has conducted clinical trials for AstraZeneca, Centocor, GlaxoSmithKline, Pfizer, Roche, and Sanofi. He has served as a consultant for AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, and Roche. A patent is pending on the use of PDE4 inhibitors in repair; he is coinventor of the patent owned by the University of Nebraska Medical Center.

(Received in original form March 17, 2006; accepted in final form March 28, 2006)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kobayashi, T. Articles by Rennard, S. I. Search for Related Content PubMed Articles by Kobayashi, T. Articles by Rennard, S. I.