Thrombospondin-1 is a major activator of TGF-β1 in vivo

Academic Article

Abstract

  • The activity of TGF-β1 is regulated primarily extracellularly where the secreted latent form must be modified to expose the active molecule. Here we show that thrombospondin-1 is responsible for a significant proportion of the activation of TGF-β1 in vivo. Histological abnormalities in young TGF-β1 null and thrombospondin-1 null mice were strikingly similar in nine organ systems. Lung and pancreas pathologies similar to those observed in TGF-β1 null animals could be induced in wild-type pups by systemic treatment with a peptide that blocked the activation of TGF-β1d by thrombospondin-1. Although these organs produced little active TGF-β1 in thrombospondin null mice, when pups were treated with a peptide derived from thrombospondin-1 that could activate TGF-β1, active cytokine was detected in situ, and the lung and pancreatic abnormalities reverted toward wild type.
  • Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Crawford SE; Stellmach V; Murphy-Ullrich JE; Ribeiro SMF; Lawler J; Hynes RO; Boivin GP; Bouck N
  • Start Page

  • 1159
  • End Page

  • 1170
  • Volume

  • 93
  • Issue

  • 7