title: [Role of thrombospondin-1 in the development of kidney diseases].
abstract: Thrombospondin-1 (TSP-1) is a 450-kDa matricellar glycoprotein. By its various domains, it can interact with various partners and exhibit anti-angiogenic, pro-apoptotic and immunomodulatory activities. TSP-1 is also a major endogenous activator of the pro-fibrotic growth factor TGF-β. In healthy adult renal parenchyma, TSP-1 expression is very scarce and limited to Bowman's capsule and interstitium. During nephropathies, many cell types can express or secrete TSP-1 (mesangial, endothelial, smooth muscle, tubular cells, podocytes and fibroblasts) depending on the nature of injury and the evolutive stage of the disease. Inhibition of the different domains of TSP-1 using specific antibodies or peptides, blockade of TSP-1 expression by antisense oligonucleotides and use of knock-out mice, allowed to identify the role of TSP-1 in various models of experimental nephropathy. All these studies demonstrated a deleterious effect of TSP-1 on renal repair by inducing TGF-β and fibrosis, decreasing VEGF and capillary density, and enhancing inflammatory cells recruitment. Thus, TSP-1 represents a potential therapeutic target for the management of chronic kidney diseases.
authors.affiliation: Service néphrologie et dialyse, Inserm UMRS 702, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.
authors.forename: Naïke
authors.initials: N
authors.lastname: Bigé
authors.affiliation: Service néphrologie et dialyse, Inserm UMRS 702, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: Service néphrologie et dialyse, Inserm UMRS 702, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lepeytre
authors.affiliation: Service néphrologie et dialyse, Inserm UMRS 702, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.
authors.forename: Nasim
authors.initials: N
authors.lastname: Shweke
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D006801:Humans; D056747:Immunomodulation / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta