Adrenergic Receptor Signaling Pathways in the Regulation of Apoptosis and Autophagy in the Heart

MacLean, Jessica; Pasumarthi, Kishore B.S.

doi:10.1007/978-3-030-78799-8_2

Cited by 1 publication

(1 citation statement)

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“…Treatment with relaxin specifically reverses cardiac fibrosis in the cardiomyopathy or hypertrophy fibrosis animal models (Bathgate et al, 2008;Parikh et al, 2013;Sun et al, 2019). Several reviews focusing on the relaxin and their protective roles in cardiac fibrosis have published in recent years (Barker, Tan, & Clevers, 2013;Devarakonda & Salloum, 2018;Du, Bathgate, Samuel, Dart, & Summers, 2010;MacLean & Pasumarthi, 2014;Martin et al, 2019;Ng et al, 2018;Sarwar, Du, Dschietzig, & Summers, 2017;van der Westhuizen et al, 2008). Lower levels of circulating relaxin were reported in patients with heart failure and hypertension (Gedikli et al, 2009;Kupari, Mikkola, Turto, & Lommi, 2005).…”

Section: Cardiac Fibrosismentioning

confidence: 99%

The relaxin family peptide receptor 1 (RXFP1): An emerging player in human health and disease

Chen

Hung

et al. 2020

Molec Gen & Gen Med

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Background: Relaxin/relaxin family peptide receptor 1 (RXFP1) signaling is important for both normal physiology and disease. Strong preclinical evidence supports relaxin as a potent antifibrotic molecule. However, relaxin-based therapy failed in clinical trial in patients with systemic sclerosis. We and others have discovered that aberrant expression of RXFP1 may contribute to the abnormal relaxin/RXFP1 signaling in different diseases. Reduced RXFP1 expression and alternative splicing transcripts with potential functional consequences have been observed in fibrotic tissues.A relative decrease in RXFP1 expression in fibrotic tissues-specifically lung and skin-may explain a potential insensitivity to relaxin. In addition, receptor dimerization also plays important roles in relaxin/RXFP1 signaling. Methods: This review describes the tissue specific expression, characteristics of the splicing variants, and homo/heterodimerization of RXFP1 in both normal physiological function and human diseases. We discuss the potential implications of these molecular features for developing therapeutics to restore relaxin/RXFP1 signaling and to harness relaxin's potential antifibrotic effects. Results: Relaxin/RXFP1 signaling is important in both normal physiology and in human diseases. Reduced expression of RXFP1 in fibrotic lung and skin tissues surrenders both relaxin/RXFP1 signaling and their responsiveness to exogenous relaxin treatments. Alternative splicing and receptor dimerization are also important in regulating relaxin/RXFP1 signaling. Conclusions: Understanding the molecular mechanisms that drive aberrant expression of RXFP1 in disease and the functional roles of alternative splicing and receptor dimerization will provide insight into therapeutic targets that may restore the relaxin responsiveness of fibrotic tissues. K E Y W O R D S alternative splicing, fibrosis, relaxin, RXFP1While much is known about the cell signaling pathways activated by relaxin, it is clear that ligand-receptor interactions are multidimensional and represent a potential site for cell signaling regulation. In experimental binding assays, relaxin dose, treatment length, and assay temperature contributed to the efficiency of relaxin binding to its receptor (Svendsen

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