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Fibroblast growth factor-2, but not the adipose tissue-derived stromal cells secretome, inhibits TGF-beta 1-induced differentiation of human cardiac fibroblasts into myofibroblasts

Aquinas Liguori, T. T., Liguori, G. R., Pinho Moreira, L. F. & Harmsen, M. C., 9-Nov-2018, In : Scientific Reports. 8, 1, 10 p., 16633.

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Transforming growth factor-beta 1 (TGF-beta 1) is a potent inducer of fibroblast to myofibroblast differentiation and contributes to the pro-fibrotic microenvironment during cardiac remodeling. Fibroblast growth factor-2 (FGF-2) is a growth factor secreted by adipose tissue-derived stromal cells (ASC) which can antagonize TGF-beta 1 signaling. We hypothesized that TGF-beta 1-induced cardiac fibroblast to myofibroblast differentiation is abrogated by FGF-2 and ASC conditioned medium (ASC-CMed). Our experiments demonstrated that TGF-beta 1 treatment-induced cardiac fibroblast differentiation into myofibroblasts, as evidenced by the formation of contractile stress fibers rich in alpha SMA. FGF-2 blocked the differentiation, as evidenced by the reduction in gene (TAGLN, p <0.0001; ACTA2, p = 0.0056) and protein (alpha SMA, p = 0.0338) expression of mesenchymal markers and extracellular matrix components gene expression (COL1A1, p <0.0001; COL3A1, p = 0.0029). ASC-CMed did not block myofibroblast differentiation. The treatment with FGF-2 increased matrix metalloproteinases gene expression (MMP1, p <0.0001; MMP14, p = 0.0027) and decreased the expression of tissue inhibitor of metalloproteinase gene TIMP2 (p = 0.0023). ASC-CMed did not influence these genes. The proliferation of TGF-beta 1-induced human cardiac fibroblasts was restored by both FGF-2 (p = 0.0002) and ASC-CMed (p = 0.0121). The present study supports the anti-fibrotic effects of FGF-2 through the blockage of cardiac fibroblast differentiation into myofibroblasts. ASC-CMed, however, did not replicate the anti-fibrotic effects of FGF-2 in vitro.

Original languageEnglish
Article number16633
Number of pages10
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 9-Nov-2018

    Keywords

  • MESENCHYMAL STEM-CELLS, CHRONIC MYOCARDIAL-INFARCTION, HUMAN DERMAL FIBROBLASTS, TGF-BETA, ISCHEMIC CARDIOMYOPATHY, SIGNALING PATHWAYS, COLLAGEN-SYNTHESIS, PARACRINE ACTIONS, IN-VIVO, EXPRESSION

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