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Connective tissue remodeling is achieved by a complex process involving several cell types, a plethora of growth factors, cytokines, chemokines and turnover of extracellular matrix (ECM). The main enzymes that degrade ECM molecules are matrix metalloproteinases (MMPs) and their activities are regulated by endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recent studies have indicated that endothelins and their receptor expression affects tissue remodeling and repair. Endothelins are rapidly produced by endothelial cells in response to tissue injury and they have potent vasoconstrictive properties. They also promote tissue remodeling through activation of resident connective tissue cells and controlling the production of MMPs and TIMPs by the activated cells. In this review we present the cross-talk between the endothelins and the MMP-TIMP system and their implications in controlling the normal and abnormal tissue remodeling.

Original publication

DOI

10.2174/157016105774329480

Type

Journal article

Journal

Current vascular pharmacology

Publication Date

10/2005

Volume

3

Pages

369 - 379

Addresses

Centre for Rheumatology and Connective Tissue Diseases, Department of Medicine, Royal Free and University College Medical School, London, UK. dabraham@medsch.ucl.ac.uk

Keywords

Connective Tissue, Extracellular Matrix, Animals, Humans, Matrix Metalloproteinases, Endothelins, Receptors, Endothelin, Tissue Inhibitor of Metalloproteinases, Regeneration, Signal Transduction