Fibroblast migration after myocardial infarction is regulated by transient SPARC expression
Copyright policy )Fibroblast migration after myocardial infarction is regulated by transient SPARC expression
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 alpha(v) 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 alpha(v) 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 alpha(v) 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.
- University of Würzburg Germany
- University of Konstanz Germany
Male, Integrins, Myocardial Infarction, Transforming Growth Factor beta1, Tissue remodeling, Mice, Cell Movement, Transforming Growth Factor beta, Animals, Cell migration, Myocytes, Cardiac, Osteonectin, Vitronectin, Cells, Cultured, info:eu-repo/classification/ddc/570, Platelet-Derived Growth Factor, Extracellular Matrix Proteins, Extracellular matrix, Fibroblasts, Fibronectins, Mice, Inbred C57BL, Myocardial infarction, Gene Expression Regulation, Female, Integrin alpha Chains
Male, Integrins, Myocardial Infarction, Transforming Growth Factor beta1, Tissue remodeling, Mice, Cell Movement, Transforming Growth Factor beta, Animals, Cell migration, Myocytes, Cardiac, Osteonectin, Vitronectin, Cells, Cultured, info:eu-repo/classification/ddc/570, Platelet-Derived Growth Factor, Extracellular Matrix Proteins, Extracellular matrix, Fibroblasts, Fibronectins, Mice, Inbred C57BL, Myocardial infarction, Gene Expression Regulation, Female, Integrin alpha Chains
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