期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 301, 期 5, 页码 L683-L692出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00187.2011
关键词
collagenase; proteolysis; extracellular matrix
资金
- NIH [CA71699]
- Breast Cancer Research Foundation
- MDRTC Cell and Molecular Biology Core NIH [P60 DK020572]
Rowe RG, Keena D, Sabeh F, Willis AL, Weiss SJ. Pulmonary fibroblasts mobilize the membrane-tethered matrix metalloprotease, MT1-MMP, to destructively remodel and invade interstitial type I collagen barriers. Am J Physiol Lung Cell Mol Physiol 301: L683-L692, 2011. First published August 12, 2011; doi:10.1152/ajplung.00187.2011.-In acute and chronic lung disease, widespread disruption of tissue architecture underlies compromised pulmonary function. Pulmonary fibroblasts have been implicated as critical effectors of tissue-destructive extracellular matrix (ECM) remodeling by mobilizing a spectrum of proteolytic enzymes. Although efforts to date have focused on the catabolism of type I collagen, the predominant component of the lung interstitial matrix, the key collagenolytic enzymes employed by pulmonary fibroblasts remain unidentified. Herein, membrane type-1 matrix metalloprotease (MT1-MMP) is identified as the dominant and direct-acting protease responsible for the type I collagenolytic activity mediated by both mouse and human pulmonary fibroblasts. Furthermore, MT1-MMP is shown to be essential for pulmonary fibroblast migration within three-dimensional (3-D) hydrogels of cross-linked type I collagen that recapitulate ECM barriers encountered in the in vivo environment. Together, these findings demonstrate that MT1-MMP serves as a key effector of type I collagenolytic activity in pulmonary fibroblasts and earmark this pericellular collagenase as a potential target for therapeutic intervention.
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