+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Coordinated effects of fibroblast growth factor-2 on expression of fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases by human vascular smooth muscle cells. Evidence for repressed collagen production and activated degradative capacity



Coordinated effects of fibroblast growth factor-2 on expression of fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases by human vascular smooth muscle cells. Evidence for repressed collagen production and activated degradative capacity



Arteriosclerosis, Thrombosis, and Vascular Biology 17(3): 475-482



Fibroblast growth factor-2 (FGF-2) is an established mediator of smooth muscle cell (SMC) proliferation after vascular injury. However, the influence of FGF-2 on collagen fiber remodeling, which may be a prerequisite for vascular SMC accumulation, is not well understood. We determined that FGF-2 almost completely abrogated the formation of immunodetectable type I collagen fibers in the extracellular matrix of cultured human vascular SMCs. This was associated with reduced expression of pro-alpha-chains for types I and III collagen, as assessed by Western blot analysis, and a corresponding reduction in collagen synthesis. Densitometry of Northern blots indicated a potent reduction of mRNA encoding pro-alpha-chains for types I and III collagen and a minor reduction in mRNA for pro-alpha-chains for type V collagen. Interstitial collagenase (MMP-1), which is required for degradation of collagen types I and III, was not expressed by SMCs under basal culture conditions, but expression was induced by FGF-2, with a potent, dose-dependent increase in MMP-1 protein in conditioned medium. Metalloproteinase inhibitors TIMP-1, TIMP-2, and TIMP-3 were expressed by unstimulated SMCs and were differentially regulated by FGF-2. TIMP-1 expression increased modestly, TIMP-2 expression was repressed, and TIMP-3 was relatively unaffected. The net effect on substrate degradation, as assessed by zymography of conditioned media, was induction of MMP-1 lytic activity by FGF-2, with no effect on the activity of MMP-2, MMP-3, or MMP-9. These data indicate that stimulation of human SMCs with FGF-2 establishes a phenotype in which collagen fiber production is repressed and the capacity for fiber degradation activated. This coordinated response may be critical for SMC accumulation during vascular remodeling as well as atherosclerotic plaque destabilization.

(PDF emailed within 1 workday: $29.90)

Accession: 008388935

Download citation: RISBibTeXText

PMID: 9102165


Related references

Effects of tumor necrosis factor-alpha on the synthesis of DNA, the secretion of matrix metalloproteinases/tissue inhibitors of metalloproteinases, and the activity of invasive migration in cultured vascular smooth muscle cells. Journal of Health Science 48(4): 354-358, 2002

Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by basic fibroblast growth factor and dexamethasone in periodontal ligament cells. Journal of Periodontal Research 44(6): 794-802, 2010

Role of fibroblast growth factor-2 in the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human intestinal myofibroblasts. Digestion 69(1): 34-44, 2004

Endovascular treatment of aneurysms: healing mechanisms in a Swine model are associated with increased expression of matrix metalloproteinases, vascular cell adhesion molecule-1, and vascular endothelial growth factor, and decreased expression of tissue inhibitors of matrix metalloproteinases. Ajnr. American Journal of Neuroradiology 28(5): 849-856, 2007

Differential effects of transforming growth factor-beta 1 on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in young and old human fibroblasts. Experimental Gerontology 31(1-2): 207-223, 1996

Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases and vascular endothelial growth factor in canine mast cell tumours. Journal of Comparative Pathology 147(4): 419-429, 2013

Is collagen breakdown during periodontitis linked to inflammatory cells and expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival tissue?. Journal of Periodontology 72(10): 1398-1406, 2001

Effects of Tumor Necrosis Factor Alpha on the Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Keratoconus Fibroblasts. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 33(6): 1139-1144, 2018

Human aqueous humor levels of transforming growth factor-β2: Association with matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases. Biomedical Reports 7(6): 573-578, 2017

Nicotine and cotinine stimulate secretion of basic fibroblast growth factor and affect expression of matrix metalloproteinases in cultured human smooth muscle cells. Journal Of Vascular Surgery. 24(6): 27-35, 1996

The protein expression difference of transforming growth factor beta1, matrix metalloproteinases 1,7,9 and tissue inhibitors of matrix metalloproteinases-1 between chronic rhinosinusitis, nasal polyps and normal mucosa tissues. Lin Chuang Er Bi Yan Hou Ke Za Zhi 19(14): 633-635, 2005

Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in mesothelial cells and their regulation by transforming growth factor-beta1. Wound Repair and Regeneration 7(6): 477-485, 2000

Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: Role of flt-1. Circulation Research 83(8): 832-840, Oct 19, 1998

Prevalence of vascular-endothelial growth factor, matrix metalloproteinases and tissue inhibitors of metalloproteinases in primary breast cancer. Brazilian Journal of Medical and Biological Research 42(10): 979-987, 2010

Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. Journal of Pathology 182(3): 347-355, 1997