title: Thrombospondin immune regulation and the kidney.
abstract: Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease. The effects of TSPs in the kidney have been mostly investigated by using the murine model of unilateral ureteral obstruction. In this model, TSP1 expression is increased along with the development of interstitial fibrosis and TGF-β. Relief of the obstruction gradually improves renal function and decreases the expression in TSP1 and TGF-β1. Several inhibitors of TSP1 prevented progressive interstitial fibrosis in murine models of ureteral obstruction, suggesting that control of latent TGF-β activation by inhibiting TSP1 might represent a novel potential target for preventing renal interstitial fibrosis. However, further studies are needed to assess whether TSP1-mediated TGF-β activation can be safely used in humans. In fact, TSPs normally act to suppress tumors in vivo. Moreover, TGF-β can exert a pivotal function in the immune system, as it may induce the production of regulatory T cells and suppress B cell responses. Knowledge of the molecular mechanisms involved in TGF-β regulation may help in finding effective treatments of tissue fibrosis, cancer and autoimmune disease.
authors.affiliation: Renal Unit, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ponticelli
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019699:Thrombospondins / Q000276:immunology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D019699:Thrombospondins; D053773:Transforming Growth Factor beta1
keywords: angiogenesis; chronic kidney disease; renal interstitial fibrosis; thrombospondin; trasforming growth factor