Differential expression of thrombospondin and cellular fibronectin during remodeling in proliferative glomerulonephritis

Jeffrey L. Barnes, Ronda J. Mitchell, John J. Kanalas, Veronique L. Barnes

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalJournal of Histochemistry and Cytochemistry
Volume47
Issue number4
DOIs
StatePublished - Apr 1999

Keywords

  • Alternatively spliced fibronectin
  • Extracellular matrix
  • Mesangial cell
  • Migration
  • Proliferation
  • Thrombospondin

ASJC Scopus subject areas

  • Anatomy
  • Histology

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