Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts

H. Laeremans, S.S.M. Rensen, H.C.J. Ottenheijm, J.F.M. Smits, W.M. Blankesteijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The Wnt/frizzled (Fzd) signal transduction cascade has been implicated in the proliferation, differentiation, and migration of many cell types, but the role of this pathway in cardiac fibroblast differentiation is not known. Our lab previously showed an up-regulation of Fzd-1 and -2 expression in myofibroblasts after myocardial infarction (MI), indicating a potential role for the Fzd receptor in fibroblast-myofibroblast differentiation. The present study was performed to further define the role of specific Wnt and Fzd proteins in the proliferation, migration, and differentiation of cardiac fibroblasts. Because primary fibroblasts become senescent after a few passages and are difficult to transfect, we immortalized rat cardiac fibroblasts with telomerase [cardiac fibroblasts immortalized with telomerase (CFIT)]. Proliferation of CFIT was not significantly influenced by Wnt/Fzd signalling. The migration, however, was attenuated by all Wnt/Fzd combinations tested. Also, specific Wnt/Fzd combinations modulated the expression of the following myofibroblast markers: collagen I alpha 1, collagen III, fibronectin and its splice variants, and alpha-smooth muscle actin. The results indicate that myofibroblast migration and differentiation, but not proliferation, can be modulated by interventions in Wnt/Fzd signalling. Therefore, Wnt/Fzd signalling may serve as a novel therapeutic target to ameliorate wound healing after MI.
Original languageEnglish
Pages (from-to)514-523
Number of pages10
JournalCardiovascular Research
Volume87
Issue number3
DOIs
Publication statusPublished - 1 Aug 2010

Keywords

  • Myofibroblast
  • Heart
  • Wnt
  • frizzled signalling
  • Differentiation
  • Migration
  • ACUTE MYOCARDIAL-INFARCTION
  • NUCLEAR BETA-CATENIN
  • CLINICAL-IMPLICATIONS
  • ANGIOTENSIN-II
  • TISSUE-REPAIR
  • DNA-SYNTHESIS
  • RAT-HEART
  • MYOFIBROBLASTS
  • CELLS
  • TELOMERASE

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