ArticleMolecular and cellular endocrinology2010
Relaxin signaling activates peroxisome proliferator-activated receptor gamma.
Article in Molecular and cellular endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.International journal of molecular sciences · 2023Article
- Relaxin Inhibits the Cardiac Myofibroblast NLRP3 Inflammasome as Part of Its Anti-Fibrotic Actions via the Angiotensin Type 2 and ATP (P2X7) Receptors.International journal of molecular sciences · 2022Article
- Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis.Nature nanotechnology · 2021Article
- Optimization of the first small-molecule relaxin/insulin-like family peptide receptor (RXFP1) agonists: Activation results in an antifibrotic gene expression profile.European journal of medicinal chemistry · 2018Article
- Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis.World journal of gastroenterology · 2017Article
- Anti-fibrotic actions of relaxin.British journal of pharmacology · 2017Review
- Structural commonality of C1q TNF-related proteins and their potential to activate relaxin/insulin-like family peptide receptor 1 signalling pathways in cancer cells.British journal of pharmacology · 2017Review
- Novel Anti-fibrotic Therapies.Frontiers in pharmacology · 2017Review
- Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α).The Journal of biological chemistry · 2015Article
- International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides.Pharmacological reviews · 2015Review
- The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Review
- Dominant-negative and knockdown approaches to studying PPAR activity.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Determination of PPARγ activity in adipose tissue and spleen.Journal of immunoassay & immunochemistry · 2012Article
- Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-γ.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
- Effect of PPARγ inhibition during pregnancy on posterior cerebral artery function and structure.Frontiers in physiology · 2010Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Relaxin is a polypeptide hormone that triggers multiple signaling pathways through its receptor RXFP1 (relaxin family peptide receptor 1). Many of relaxin's functions, including vascular and antifibrotic effects, are similar to those induced by activation of PPARgamma. In this study, we tested the hypothesis that relaxin signaling through RXFP1 would activate PPARgamma activity. In cells overexpressing RXFP1 (HEK-RXFP1), relaxin increased transcriptional activity through a PPAR response element (PPRE) in a concentration-dependent manner. In cells lacking RXFP1, relaxin had no effect. Relaxin increased both the baseline activity and the response to the PPARgamma agonists rosiglitazone and 15d-PGJ(2), but not to agonists of PPARalpha or PPARdelta. In HEK-RXFP1 cells infected with adenovirus expressing PPARgamma, relaxin increased transcriptional activity through PPRE, and this effect was blocked with an adenovirus expressing a dominant-negative PPARgamma. Knockdown of PPARgamma using siRNA resulted in a decrease in the response to both relaxin and rosiglitazone. Both relaxin and rosiglitazone increased expression of the PPARgamma target genes CD36 and LXRalpha in HEK-RXFP1 and in THP-1 cells naturally expressing RXFP1. Relaxin did not increase PPARgamma mRNA or protein levels. Treatment of cells with GW9662, an inhibitor of PPARgamma ligand binding, effectively blocked rosiglitazone-induced PPARgamma activation, but had no effect on relaxin activation of PPARgamma. These results suggest that relaxin activates PPARgamma activity, and increases the overall response in the presence of PPARgamma agonists. This activation is dependent on the presence of RXFP1. Furthermore, relaxin activates PPARgamma via a ligand-independent mechanism. These studies represent the first report that relaxin can activate the transcriptional activity of PPARgamma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.