Thrombospondin-1 is a major activator of TGF-beta1 in vivo

Cell. 1998 Jun 26;93(7):1159-70. doi: 10.1016/s0092-8674(00)81460-9.


The activity of TGF-beta1 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-beta1 in vivo. Histological abnormalities in young TGF-beta1 null and thrombospondin-1 null mice were strikingly similar in nine organ systems. Lung and pancreas pathologies similar to those observed in TGF-beta1 null animals could be induced in wild-type pups by systemic treatment with a peptide that blocked the activation of TGF-beta1 by thrombospondin-1. Although these organs produced little active TGF-beta1 in thrombospondin null mice, when pups were treated with a peptide derived from thrombospondin-1 that could activate TGF-beta1, active cytokine was detected in situ, and the lung and pancreatic abnormalities reverted toward wild type.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Coculture Techniques
  • Epithelial Cells
  • Fibroblasts
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Oligopeptides / pharmacology
  • Pancreas / pathology
  • Peptide Fragments*
  • Protein Precursors*
  • Proteins / pharmacology
  • Skin / cytology
  • Thrombospondin 1 / physiology*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta1


  • Oligopeptides
  • Peptide Fragments
  • Protein Precursors
  • Proteins
  • Thrombospondin 1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1