PURPOSE: This investigation was designed to test the hypothesis that transforming growth factor-beta 1 (TGF-beta 1) regulates lysyl oxidase secretion from vascular smooth muscle cells. Lysyl oxidase is an enzyme that catalyzes an essential step in collagen and elastin cross-linking in the extracellular matrix, and TGF-beta 1 has been implicated in the pathogenesis of restenosis after vascular injury. The effect of TGF-beta 1 on lysyl oxidase in vascular smooth muscle cells has not been previously defined. METHODS: Rat aortic smooth muscle cells were grown in culture to confluence. Cells in passage 2 to 6 were incubated for 24 hours in media containing 0.1, 0.5, 1.0, or 10.0 ng/ml of TGF-beta 1. Lysyl oxidase activity in the media was quantitated with a tritium-release bioassay against an insoluble 3H-labeled aortic clastin substrate. Northern blot analyses were performed to determine steady-state levels of lysyl oxidase mRNA in the smooth muscle cells. RESULTS: Lysyl oxidase activity in the media increased 1.5-fold above control levels after exposure to 10 ng/ml of TGF-beta 1 (p < 0.01). This increase in lysyl oxidase activity was associated with a concentration-dependent increase in steady-state levels of lysyl oxidase mRNA, being 4.3- and 6.2-fold above control levels after exposure to 1 and 10 ng/ml TGF-beta 1, respectively (p < 0.01). The observed increase in steady-state lysyl oxidase mRNA after exposure to TGF-beta 1 was also time-dependent over the 24-hour experimental period. CONCLUSIONS: TGF-beta 1 appears to regulate lysyl oxidase in cultured rat aortic smooth muscle cells. Increases in lysyl oxidase activity may be one of the mechanisms by which TGF-beta 1 contributes to arterial restenosis after vascular injury.
PURPOSE: This investigation was designed to test the hypothesis that transforming growth factor-beta 1 (TGF-beta 1) regulates lysyl oxidase secretion from vascular smooth muscle cells. Lysyl oxidase is an enzyme that catalyzes an essential step in collagen and elastin cross-linking in the extracellular matrix, and TGF-beta 1 has been implicated in the pathogenesis of restenosis after vascular injury. The effect of TGF-beta 1 on lysyl oxidase in vascular smooth muscle cells has not been previously defined. METHODS:Rat aortic smooth muscle cells were grown in culture to confluence. Cells in passage 2 to 6 were incubated for 24 hours in media containing 0.1, 0.5, 1.0, or 10.0 ng/ml of TGF-beta 1. Lysyl oxidase activity in the media was quantitated with a tritium-release bioassay against an insoluble 3H-labeled aortic clastin substrate. Northern blot analyses were performed to determine steady-state levels of lysyl oxidase mRNA in the smooth muscle cells. RESULTS:Lysyl oxidase activity in the media increased 1.5-fold above control levels after exposure to 10 ng/ml of TGF-beta 1 (p < 0.01). This increase in lysyl oxidase activity was associated with a concentration-dependent increase in steady-state levels of lysyl oxidase mRNA, being 4.3- and 6.2-fold above control levels after exposure to 1 and 10 ng/ml TGF-beta 1, respectively (p < 0.01). The observed increase in steady-state lysyl oxidase mRNA after exposure to TGF-beta 1 was also time-dependent over the 24-hour experimental period. CONCLUSIONS:TGF-beta 1 appears to regulate lysyl oxidase in cultured rat aortic smooth muscle cells. Increases in lysyl oxidase activity may be one of the mechanisms by which TGF-beta 1 contributes to arterial restenosis after vascular injury.
Authors: Jing Xie; Jiahuan Jiang; Yanjun Zhang; Chunming Xu; Lin Yin; Chunli Wang; Peter C Y Chen; K L Paul Sung Journal: Int Orthop Date: 2011-06-15 Impact factor: 3.075
Authors: Katarzyna A Cieslik; George E Taffet; Jeffrey R Crawford; JoAnn Trial; Patricia Mejia Osuna; Mark L Entman Journal: J Mol Cell Cardiol Date: 2013-07-19 Impact factor: 5.000