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Extracellular Matrix Gene Changes in Cardiac Fibroblasts Stimulated with Transforming Growth Factor
Author(s) -
Dai Qiuxia,
Escobar G. Patricia,
Lindsey Merry L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.903.1
Subject(s) - extracellular matrix , transforming growth factor , downregulation and upregulation , cell adhesion molecule , microbiology and biotechnology , fibroblast , gene expression , stimulation , fibrosis , chemistry , extracellular , gene , cell adhesion , biology , cell , pathology , endocrinology , biochemistry , in vitro , medicine
The cardiac fibroblast (CFbs) is the primary cell type that responds to injury stimuli by secreting extracellular matrix (ECM). Excessive ECM accumulation results in fibrosis, which can impair left ventricular (LV) function. Therefore, understanding the connection between CFb activation and ECM accumulation will provide insight into how CFbs regulate LV function. Accordingly, we examined CFb ECM gene response to TGFβ stimulation. Primary fibroblasts were isolated from the LV of C57/BL6J mice (n=4). Paired cultures were incubated in serum free media without (control) or with TGFβ (10 ng/mL) for 24 h. The mouse ECM and adhesion molecule RT2 profiler PCR array was used to determine gene expression levels of 84 ECM and adhesion molecule genes. Of these genes, 18 were differentially expressed with TGFβ stimulation. In the 7 upregulated genes, secreted protein acidic and rich in cysteine (SPARC), was the most upregulated protein, increasing 60.2% from −1.4±0.1 to −2.3±0.1 normalized threshold cycles (ΔCt) (p<0.001). In the 11 downregulated genes, tissue inhibitor of metalloproteinase 2 (TIMP‐2) and vascular cell adhesion molecule 1 (VCAM‐1) were the most downregulated proteins, decreasing 45.8% and 48.4%, respectively. Combined, these data indicate that 10ng/mL TGFβ stimulation activates a pro‐fibrotic CFb phenotype by increasing ECM gene expression.