Fibroblasts potentiate blood vessel formation partially through secreted factor TIMP-1.

作者: Hua Liu , Bo Chen , Brenda Lilly

DOI: 10.1007/S10456-008-9102-8

关键词:

摘要: During wound repair, new blood vessels form in response to angiogenic signals emanating from injured tissues. Dermal fibroblasts are known play an important role healing, and have been linked angiogenesis; therefore, we sought understand the mechanisms through which these cells control vessel formation. Using a three-dimensional angiogenesis assay demonstrate that dermal enhance tube-forming potential of endothelial cells, this augmentation is partially due secreted factors present conditioned media. Interestingly, identified tissue inhibitor metalloproteinase-1 (TIMP-1) as factor uniquely by fibroblasts, addition exogenous TIMP-1 increased assembly. The enhancing activity was matrix metalloproteinase (MMP)-dependent, since mutant version unable promote angiogenesis. Consistent with this, chemical inhibition MMP-2/9 showed similar increase angiogenesis, MMP-9 blocked effect TIMP-1. We further demonstrated inhibits production tumstatin, anti-angiogenic fragment collagen IV produced cleavage. Our results support notion regulate formation multiple mediators, provide novel evidence fibroblast-derived acts on pro-angiogenic capacity.

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