Journal article

Publication year: 2021

Journal: Cells

Volume number: 10

Issue number: 6

eISSN: 2073-4409

Open access status: Gold

DOI Link: https://doi.org/10.3390/cells10061326

Publisher: MDPI

Abstract: 
Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by mu-calpain upon myocardial injury, releasing C0-C1f, an N-terminal peptide of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is able to activate macrophages. Fibroblasts also play a crucial role in cardiac remodeling arising from ischemic events, as they contribute to both inflammation and scar formation. To understand whether C0-C1f directly modulates fibroblast phenotype, we analyzed the impact of C0-C1f on a human fibroblast cell line in vitro by performing mRNA microarray screening, immunofluorescence staining, and quantitative real-time PCR. The underlying signaling pathways were investigated by KEGG analysis and determined more precisely by targeted inhibition of the potential signaling cascades in vitro. C0-C1f induced pro-inflammatory responses that might delay TGF beta-mediated myofibroblast conversion. TGF beta also counteracted C0-C1f-mediated fibroblast activation. Inhibition of TLR4 or NF kappa B as well as the delivery of miR-146 significantly reduced C0-C1f-mediated effects. In conclusion, C0-C1f induces inflammatory responses in human fibroblasts that are mediated via TRL4 signaling, which is decreased in the presence of TGF beta. Specific targeting of TLR4 signaling could be an innovative strategy to modulate C0-C1f-mediated inflammation.

Harvard Citation style: Yogeswaran, A., Troidl, C., McNamara, J., Wilhelm, J., Truschel, T., Widmann, L., et al. (2021) The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling, Cells, 10(6), Article 1326. https://doi.org/10.3390/cells10061326

APA Citation style: Yogeswaran, A., Troidl, C., McNamara, J., Wilhelm, J., Truschel, T., Widmann, L., Aslam, M., Hamm, C., Sadayappan, S., & Lipps, C. (2021). The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling. Cells. 10(6), Article 1326. https://doi.org/10.3390/cells10061326