Differential Expression of Thrombospondin and Cellular Fibronectin During Remodeling in Proliferative Glomerulonephritis

• Published in: The journal of histochemistry and cytochemistry 1999-04, Vol.47 (4), p.533-543
• Main Authors: Barnes, Jeffrey L, Mitchell, Ronda J, Kanalas, John J, Barnes, Veronique L
• Format: Article
• Language: English
• Subjects: Animals; Cell Division; Extracellular Matrix Proteins - metabolism; Fibronectins - biosynthesis; Fibronectins - genetics; Glomerulonephritis, Membranoproliferative - metabolism; Glomerulonephritis, Membranoproliferative - pathology; Image Processing, Computer-Assisted; Immunoenzyme Techniques; In Situ Hybridization; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Thrombospondin 1 - biosynthesis; Thrombospondin 1 - genetics; Time Factors
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1177/002215549904700412

Thrombospondin-1 (TSP-1) and an alternatively spliced fibronectin (Fn)-EIIIA isoform are adhesive proteins associated with embryogenesis and tissue remodeling. We compared, by immunohistochemistry and in situ hybridization, the course of TSP-1 and Fn-EIIIA expression in a model of glomerulonephritis induced by Habu snake venom (HV) and characterized by mesangial cell migration, proliferation, and extracellular matrix (ECM) synthesis. At 24 hr after HV, TSP-1 and Fn-EIIIA proteins localized in the central aspects of lesions associated with platelets and macrophages and at the margins of lesions coinciding with mesangial cell migration (determined by Thy-1 staining). Mesangial cells at this time expressed TSP-1 but not Fn-EIIIA mRNA. TSP-1 protein and mRNA peaked in lesions at 48 hr and were associated with cell proliferation (determined by PCNA, α-smooth muscle actin phenotype, and expression of β-PDGF receptor mRNA). TSP-1 expression declined at 72 hr when expression of ECM synthesis peaked, as determined by increased expression of collagen Type IV, laminin, and TGF-β1 protein and mRNA. Mesangial cell expression of Fn-EIIIA was first observed at 48 hr and was most abundant at 72 hr after HV. Therefore, platelet-and macrophage-derived Fn-EIIIA and TSP-1 in early lesions are associated with mesangial cell migration. Mesangial cell upregulation of TSP-1 is associated with migration and proliferation but not maximal ECM accumulation, whereas mesangial cell expression of Fn-EIIIA is associated with proliferation and ECM accumulation. These results suggest distinctive temporal and spatial roles for TSP-1 and Fn-EIIIA in remodeling during glomerular disease.