Expression and function of TLR4- induced B1R bradykinin receptor on cardiac fibroblasts

Toxicology and Applied Pharmacology
Claudia Muñoz-RodríguezGuillermo Díaz-Araya

Abstract

Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels. However, whether TLR4 activation regulates bradykinin receptor expression remains unknown. CF were isolated from human, neonatal rat and adult mouse heart. B1R mRNA expression was evaluated by qRT-PCR, whereas B1R, collagen, COX-2 and iNOS protein levels were evaluated by Western Blot. NO and PGI2 were evaluated by commercial kits. We report here that in CF, TLR4 activation increased B1R mRNA and protein levels, as well as COX-2 and iNOS levels. B1R mRNA levels were also induced by interleukin-1α via its cognate receptor IL-1R1. In LPS-pretreated CF the DAKD treatment induced higher respo...Continue Reading

Citations

Jul 17, 2019·Molecular Biology Reports·Mabel CatalánGuillermo Díaz-Araya
Feb 11, 2020·Annual Review of Physiology·Michelle D Tallquist
Sep 25, 2019·Journal of Cardiovascular Development and Disease·Jianlin FengLixia Yue
Jun 26, 2021·Frontiers in Cardiovascular Medicine·Pablo Parra-FloresGuillermo Díaz-Araya

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