Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-beta 1 and TGF-beta 3

@article{citeulike:2295063, abstract = {Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of lung fibrosis. Transforming growth factor (TGF)-[beta] isoforms play a pivotal role in the production of collagen and ECM. In this study, we investigated the effects of TGF-[beta]1 and TGF-[beta]3 on the main processes controlling ECM deposition using primary human lung fibroblasts. We analyzed 1) collagen metabolism by [3H]proline incorporation, 2) matrix metalloproteinase (MMP) expression by substrate gel zymography, and 3) tissue inhibitor of metalloproteinases (TIMP) expression by Western blot analysis. TGF-[beta]1 and TGF-[beta]3 increased the percentage of secreted collagens in supernatants of primary fibroblasts from 8.0 {+/-} 1.2 (control) to 23.6 {+/-} 4.6 and 22.3 {+/-} 1.3\%, respectively. The collagen percentage in deposited ECM was increased from 5.8 {+/-} 0.3 (control) to 9.0 {+/-} 0.5 and 8.8 {+/-} 0.5\% by TGF-[beta]1 and TGF-[beta]3, respectively. Secretion of MMP-1 (interstitial collagenase) by fibroblasts was reduced by both TGF-[beta] isoforms, whereas secretion of MMP-2 (gelatinase A) was unaffected by either of the two isoforms. Both TGF-[beta] isoforms increased TIMP-1 protein expression, whereas TIMP-2 protein was decreased. We thus conclude that TGF-[beta]1 and TGF-[beta]3 are equally potent in increasing ECM deposition. Their fibrotic effect in lung fibroblasts results from 1) an increase in the secretion and deposition of total ECM and collagens, 2) a decrease in MMP-1 secretion, and 3) an increase of TIMP-1 expression.}, author = {Eickelberg, Oliver and Kohler, Eleonore and Reichenberger, Frank and Bertschin, Sybille and Woodtli, Thomas and Erne, Paul and Perruchoud, Andre P. and Roth, Michael }, citeulike-article-id = {2295063}, journal = {Am J Physiol Lung Cell Mol Physiol}, keywords = {method}, month = {May}, number = {5}, pages = {L814--824}, posted-at = {2008-01-27 16:06:26}, priority = {2}, title = {Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-beta 1 and TGF-beta 3}, url = {http://ajplung.physiology.org/cgi/content/abstract/276/5/L814}, volume = {276}, year = {1999} }

TY - JOUR ID - citeulike:2295063 L3 - citeulike-article-id:2295063 TI - Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-beta 1 and TGF-beta 3 JF - Am J Physiol Lung Cell Mol Physiol VL - 276 IS - 5 SP - L814 EP - 824 N2 - Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of lung fibrosis. Transforming growth factor (TGF)-[beta] isoforms play a pivotal role in the production of collagen and ECM. In this study, we investigated the effects of TGF-[beta]1 and TGF-[beta]3 on the main processes controlling ECM deposition using primary human lung fibroblasts. We analyzed 1) collagen metabolism by [3H]proline incorporation, 2) matrix metalloproteinase (MMP) expression by substrate gel zymography, and 3) tissue inhibitor of metalloproteinases (TIMP) expression by Western blot analysis. TGF-[beta]1 and TGF-[beta]3 increased the percentage of secreted collagens in supernatants of primary fibroblasts from 8.0 {+/-} 1.2 (control) to 23.6 {+/-} 4.6 and 22.3 {+/-} 1.3%, respectively. The collagen percentage in deposited ECM was increased from 5.8 {+/-} 0.3 (control) to 9.0 {+/-} 0.5 and 8.8 {+/-} 0.5% by TGF-[beta]1 and TGF-[beta]3, respectively. Secretion of MMP-1 (interstitial collagenase) by fibroblasts was reduced by both TGF-[beta] isoforms, whereas secretion of MMP-2 (gelatinase A) was unaffected by either of the two isoforms. Both TGF-[beta] isoforms increased TIMP-1 protein expression, whereas TIMP-2 protein was decreased. We thus conclude that TGF-[beta]1 and TGF-[beta]3 are equally potent in increasing ECM deposition. Their fibrotic effect in lung fibroblasts results from 1) an increase in the secretion and deposition of total ECM and collagens, 2) a decrease in MMP-1 secretion, and 3) an increase of TIMP-1 expression. KW - method AU - Eickelberg, Oliver AU - Kohler, Eleonore AU - Reichenberger, Frank AU - Bertschin, Sybille AU - Woodtli, Thomas AU - Erne, Paul AU - Perruchoud, Andre AU - Roth, Michael PY - 1999/05/01/ UR - http://ajplung.physiology.org/cgi/content/abstract/276/5/L814 ER -