Growth factor-dependent proliferation and invasion of muscle satellite cells require the cell-associated fibrinolytic system

Gabriella Fibbi, Silvia D'Alessio, Marco Pucci, Massimiliano Cerletti, Mario Del Rosso

Research output: Contribution to journalArticle

Abstract

The process of muscle regeneration in normal and dystrophic muscle depends on locally produced cytokines and growth factors and requires the activity of the urokinase plasminogen activator/urokinase plasminogen activator receptor/plasminogen activator inhibitor-1 system. In this study we tested the effect of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and transforming growth factor-β (TGFβ) on the fibrinolytic pattern of normal and dystrophic satellite cells, their mitogenic and motogenic activities and the dependence of such activities on the cell-associated fibrinolytic system. We have observed that the urokinase plasminogen activator (u-PA) receptor is weakly upregulated by bFGF in normal satellite cells, while it is strongly up-regulated by TGFβ, mainly in dystrophic myoblasts. bFGF up-regulated u-PA in both normal and dystrophic myoblasts grown in primary culture, while a striking down-regulation was observed with TGFβ. TGFβ was the only growth factor able to exceptionally up-regulate plasminogen activator inhibitor-1 (PAI-1), mainly in dystrophic satellite cells. HGF did not show any activity on the fibrinolytic system. Proliferation and invasion into Matrigel matrices of normal and dystrophic cells occurred regardless of the growth factor-dependent regulation of the fibrinolytic system. Nevertheless, each growth factor required the efficiency of the constitutive cell-associated fibrinolytic system to operate, as shown by impairment of growth factor activity with antagonists of u-PA and of its receptor. Noteworthy, TGFβ induced a dose-dependent increase of Matrigel invasion only in dystrophic myoblasts. Since TGFβ-challenged dystrophic myoblasts undergo an exceptional up-regulation of the receptor and of PAI-1, we propose the possibility that the TGFβ-induced fibrinolytic pattern (low urokinase plasminogen activator, high receptor and high PAI-1) may be exploited to promote survival and spreading of transplanted engineered myoblasts in Duchenne muscular dystrophy.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalBiological Chemistry
Volume383
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Growth factors
  • Myoblasts
  • PAl-1
  • Satellite cells
  • u-PA
  • u-PAR

ASJC Scopus subject areas

  • Biochemistry

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