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Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2013 Nov 01; Vol. 305 (9), pp. H1363-72. Date of Electronic Publication: 2013 Aug 30. - Publication Year :
- 2013
-
Abstract
- Understanding the role of fibroblasts in pathologic conditions is hampered by the absence of specific markers. Fibroblast-specific protein (FSP)1 has been suggested as a fibroblast-specific marker in normal and fibrotic tissues; FSP1 reporter mice and FSP1-Cre-driven gene deletion are considered reliable strategies to investigate fibroblast biology. Because fibroblasts are abundant in normal and injured mammalian hearts, we studied the identity of FSP1(+) cells in the infarcted and remodeling myocardium using mice with green fluorescent protein (GFP) expression driven by the FSP1 promoter. Neonatal and adult mouse hearts had low numbers of FSP1(+) cells. Myocardial infarction induced marked infiltration with FSP1-expressing cells that peaked after 72 h of reperfusion. Using flow cytometry, we identified 50% of FSP1(+) cells as hematopoietic cells; many endothelial cells were also FSP1(+). Increased infiltration with FSP1(+) cells was also noted in the pressure-overloaded myocardium. Although some FSP1(+) cells had fibroblast morphology, >30% were identified as hematopoietic cells, endothelial cells, or vascular smooth muscle cells. In contrast, periostin did not stain leukocytes or vascular cells but labeled spindle-shaped interstitial cells and, as a typical matricellular protein, was deposited in the matrix. CD11b(+) myeloid cells sorted from the infarcted heart had higher FSP1 expression than corresponding CD11b-negative cells, highlighting the predominant expression by hematopoietic cells. FSP1 is not a specific marker for fibroblasts in cardiac remodeling and fibrosis.
- Subjects :
- Animals
Biomarkers metabolism
CD11b Antigen metabolism
Cell Adhesion Molecules metabolism
Disease Models, Animal
Fibroblasts pathology
Fibrosis
Genes, Reporter
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Myocardial Infarction genetics
Myocardial Infarction pathology
Myocardial Reperfusion Injury genetics
Myocardial Reperfusion Injury pathology
Myocardium pathology
Promoter Regions, Genetic
S100 Calcium-Binding Protein A4
S100 Proteins deficiency
S100 Proteins genetics
Fibroblasts metabolism
Myocardial Infarction metabolism
Myocardial Reperfusion Injury metabolism
Myocardium metabolism
S100 Proteins metabolism
Ventricular Remodeling
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 305
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 23997102
- Full Text :
- https://doi.org/10.1152/ajpheart.00395.2013