title: Fibroblast migration after myocardial infarction is regulated by transient SPARC expression.
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 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.
authors.affiliation: Department of Medicine I, Center for Cardiovascular Medicine, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
authors.forename: Rong Xue
authors.initials: RX
authors.lastname: Wu
authors.forename: Martin
authors.initials: M
authors.lastname: Laser
authors.forename: Hong
authors.initials: H
authors.lastname: Han
authors.forename: Jeeva
authors.initials: J
authors.lastname: Varadarajulu
authors.forename: Kai
authors.initials: K
authors.lastname: Schuh
authors.forename: Matthias
authors.initials: M
authors.lastname: Hallhuber
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
authors.forename: Oliver
authors.initials: O
authors.lastname: Ritter
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D039001:Integrin alpha Chains / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015676:Osteonectin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039001:Integrin alpha Chains; D016023:Integrins; D015676:Osteonectin; D010982:Platelet-Derived Growth Factor; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019096:Vitronectin