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Fibroblast migration after myocardial infarction is regulated by transient SPARC expression

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Abstract

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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Acknowledgements

This work was supported by grants to OR by the German Research Foundation (DFG Ri 1085/3-1) and to OR and ML and CRH by the Interdisciplinary Centre for Clinical Research Würzburg [IZKF E-25(1) and Z-4/47], respectively.

Rong Xue Wu and Martin Laser contributed equally to this work.

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Authors and Affiliations

  1. Department of Medicine I, Center for Cardiovascular Medicine, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany

    Rong Xue Wu, Martin Laser, Hong Han, Matthias Hallhuber, Kai Hu, Georg Ertl & Oliver Ritter

  2. Zentrum für Infektionsforschung, University of Würzburg, Würzburg, Germany

    Jeeva Varadarajulu & Christof R. Hauck

  3. Institute for Clinical Biochemistry, University of Würzburg, Würzburg, Germany

    Kai Schuh

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  1. Rong Xue Wu
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  2. Martin Laser
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  3. Hong Han
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Correspondence to Oliver Ritter.

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Wu, R.X., Laser, M., Han, H. et al. Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. J Mol Med 84, 241–252 (2006). https://doi.org/10.1007/s00109-005-0026-0

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