Fibroblast migration after myocardial infarction is regulated by transient SPARC expression

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2006
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Wu, Rongxue
Laser, Martin
Han, Hong
Varadarajulu, Jeeva
Schuh, Kai
Hallhuber, Matthias
Hu, Kai
Ertl, Georg
Ritter, Oliver
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Journal of Molecular Medicine. 2006, 84(3), pp. 241-252. ISSN 0946-2716. eISSN 1432-1440. Available under: doi: 10.1007/s00109-005-0026-0
Zusammenfassung

Secreted protein, acidic, and rich in cysteine (SPARC) is thought to regulate cell matrix interaction during wound repair. We hypothesized that SPARC might promote migration via integrin-dependent mechanisms. The present study was designed to clarify the contribution of SPARC in the wound healing process after myocardial infarction (MI). Adult mice received a specific αv integrin inhibitor or vehicle through osmotic mini pumps. Mice of each group were either sham-operated or MI was induced. SPARC expression was investigated 2 days, 7 days, and 1 month after the surgical procedure. For migration assays, a modified Boyden chamber assay was used. A transient increase of SPARC levels was observed, starting at day 2 (2.55±0.21), day 7 (3.72±0.28), and 1 month (1.9±0.16) after MI. After 2 months, SPARC expression dropped back to normal levels compared to sham-operated hearts. Immunofluorescence analysis showed an increase of SPARC in the infarcted area 2 days after MI, a strong increase in the scar area 7 days after MI, and only low levels in the scar area 2 months after MI. Integrin αv inhibition abolished the up-regulation of SPARC. In vitro migration assays demonstrated that fibronectin-stimulated haptotaxis of fibroblasts was modulated by SPARC. This study provides evidence that SPARC is significantly up-regulated in the infarcted region after MI. This up-regulation is dependent on αv integrins. As SPARC is found to regulate fibroblast migration, it appears to play an important role in the injured myocardium with regard to healing and scar formation.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Myocardial infarction, Tissue remodeling, Extracellular matrix, Cell migration
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Rezension
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ISO 690WU, Rongxue, Martin LASER, Hong HAN, Jeeva VARADARAJULU, Kai SCHUH, Matthias HALLHUBER, Kai HU, Georg ERTL, Christof R. HAUCK, Oliver RITTER, 2006. Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. In: Journal of Molecular Medicine. 2006, 84(3), pp. 241-252. ISSN 0946-2716. eISSN 1432-1440. Available under: doi: 10.1007/s00109-005-0026-0
BibTex
@article{Wu2006Fibro-7873,
  year={2006},
  doi={10.1007/s00109-005-0026-0},
  title={Fibroblast migration after myocardial infarction is regulated by transient SPARC expression},
  number={3},
  volume={84},
  issn={0946-2716},
  journal={Journal of Molecular Medicine},
  pages={241--252},
  author={Wu, Rongxue and Laser, Martin and Han, Hong and Varadarajulu, Jeeva and Schuh, Kai and Hallhuber, Matthias and Hu, Kai and Ertl, Georg and Hauck, Christof R. and Ritter, Oliver}
}
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