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The transcriptional regulation of periostin by scleraxis in cardiac myofibroblasts
Author(s) -
Czubryt Michael P,
Nagalingam Raghu S,
Schwartz Leah Y,
AlHattab Danah S,
Aroutiounova Nina
Publication year - 2019
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.2019.33.1_supplement.532.17
Subject(s) - periostin , myofibroblast , matricellular protein , microbiology and biotechnology , cardiac fibrosis , extracellular matrix , biology , lysyl oxidase , transcription factor , ctgf , fibrosis , cancer research , growth factor , pathology , gene , medicine , genetics , receptor
Extracellular matrix (ECM) remodeling resulting in cardiac fibrosis is a crucial factor in determining the severity of myocardial dysfunction during heart failure. In response to stress or damage, cardiac fibroblasts undergo phenotype conversion to myofibroblasts, the primary cell type responsible for ECM synthesis and remodeling in the heart. Periostin, a marker of the myofibroblast phenotype, is a matricellular secreted protein that contributes to cardiac remodeling. Periostin plays important roles in mediating cell–matrix signal transduction and in promoting pro‐fibrotic TGF‐β signaling via coupling with matrix associated lysyl oxidase; it is highly expressed in myofibroblasts, but is not expressed in fibroblasts. We have shown that the transcription factor scleraxis induces the phenotype conversion of cardiac fibroblasts to myofibroblasts by directly transactivating the expression of proteins highly up‐regulated in myofibroblasts, including collagen 1α2, fibronectin and α‐smooth muscle actin. Here we report that the treatment of primary adult rat cardiac myofibroblasts with angiotensin II significantly increases periostin gene expression in parallel with increased scleraxis expression. Over‐expression of scleraxis in myofibroblasts increased periostin expression nearly 19‐fold at the mRNA level. TGF‐b treatment induced periostin expression in cardiac myofibroblasts isolated from wild type mice, but failed to show a similar effect in cells isolated from scleraxis null mice. Using in silico analysis, we identified putative E‐box sites within the periostin gene promoter to which scleraxis may bind to potentially regulate promoter transactivation. Our data suggests that scleraxis is necessary and sufficient for TGF‐β mediated periostin expression. Our findings are consistent with a potential role for scleraxis in cardiac fibrosis, where periostin and fibrillar collagen gene expression are elevated in parallel with scleraxis. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .