title: The role of thrombospondin (TSP)-1 in obesity and diabetes.
abstract: Matricellular proteins are extracellular macromolecules that do not serve a structural role, but when incorporated into the matrix, modulate cell:cell and cell:matrix interactions. The matricellular protein thrombospondin (TSP)-1, a potent angiostatic mediator and activator of transforming growth factor (TGF)-β, is upregulated in diabetes and obesity and may be involved in the pathogenesis of metabolic dysregulation and organ dysfunction. This manuscript discusses recently published observations on the role of TSP-1 in metabolic disease. In obesity models induced by a high-fat diet, adipose tissue TSP-1 upregulation induces inflammation and promotes weight gain and metabolic dysfunction. TSP-1 may have direct effects on adipocyte proliferation and fatty acid uptake. In diabetic subjects, TSP-1 upregulation in kidney, myocardium, and vascular tissue may promote dysfunction. In the myocardium, TSP-1 upregulation may transduce angiostatic signals inducing vascular rarefaction. Dissection of the functional domains involved in TSP-1 actions may lead to the development of peptide-based strategies for treatment of diabetes and its complications.
authors.affiliation: The Wilf Family Cardiovascular Research Institute; Department of Medicine (Cardiology); Albert Einstein College of Medicine; Bronx, NY USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Kong
authors.affiliation: The Wilf Family Cardiovascular Research Institute; Department of Medicine (Cardiology); Albert Einstein College of Medicine; Bronx, NY USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavalera
authors.affiliation: The Wilf Family Cardiovascular Research Institute; Department of Medicine (Cardiology); Albert Einstein College of Medicine; Bronx, NY USA.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
keywords: adipocyte; angiogenesis; diabetes; extracellular matrix; inflammation; matricellular protein; myocardium; obesity; transforming growth factor-β