Laboratory Investigation

Kidney International (1995) 48, 1846–1856; doi:10.1038/ki.1995.483

Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo

Christian Hugo1, Raimund Pichler1, Rick Meek1, Katherine Gordon1, Themis Kyriakides1, Jürgen Floege1, Paul Bornstein1, William G Couser1 and Richard J Johnson1

1Division of Nephrology, Department of Medicine and the Department of Biochemistry, University of Washington, Seattle, Washington, USA

Correspondence: Christian Hugo MD, Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Box 356521, Seattle, Washington 98195-6521, USA.

Received 20 June 1995; Revised 7 August 1995; Accepted 7 August 1995.

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Abstract

Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo. Thrombospondin 1 has been shown to be linked to PDGF-mediated mesangial cell proliferation and migration in vitro, but little is known regarding its expression or regulation in glomerular disease. Experimental mesangial proliferative nephritis was induced in rats by injection of anti-Thy1 antibody. Mesangial cell proliferation was associated with de novo expression of thrombospondin 1 mRNA (detected by Northern blot and in situ hybridization) and protein (by Western blot and immunostaining). Although some thrombospondin 1 was expressed by platelets and macrophages, double labeling showed that most thrombospondin 1 mRNA and protein were expressed by proliferating alpha-actin-positive mesangial cells. Thrombospondin 1 expression in anti-Thy1 nephritis was complement-dependent and could be reduced by treatment with anti-PDGF or anti-bFGF antibodies. Thrombospondin 1 could also be induced in normal rats by infusion of PDGF and in rats which were primed with low dose anti-Thy1 antibody by infusion of PDGF or bFGF. Thus, this study demonstrates that proliferating mesangial cells express thrombospondin 1 de novo in disease and that thrombospondin 1 expression in vivo is regulated by PDGF and bFGF.

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