ArticleKidney international2014
Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis.
Article in Kidney international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 121 citations in OpenAlex.
- Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study.Journal of the American Heart Association · 2024Trial
- The novel AT2 receptor ligand, β-Pro7 Ang III, induces equivalent anti-fibrotic effects to Compound 21 but broader anti-fibrotic effects than pirfenidone in mice with bleomycin-induced pulmonary fibrosis.Clinical science (London, England : 1979) · 2025Article
- G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes.Cells · 2025Review
- GPCR dimerization: Drug discovery aspects and targets in renin-angiotensin systems.FASEB bioAdvances · 2025Review
- Long-acting relaxin analogues: a novel tool in cardiology.Frontiers in pharmacology · 2025Review
- Engineering a long acting, non-biased relaxin agonist using Protein-in-Protein technology.Biochemical pharmacology · 2024Article
- Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.Circulation research · 2023Review
- A Lipidated Single-B-Chain Derivative of Relaxin Exhibits Improved In Vitro Serum Stability without Altering Activity.International journal of molecular sciences · 2023Article
- Relaxin in fibrotic ligament diseases: Its regulatory role and mechanism.Frontiers in cell and developmental biology · 2023Review
- The Novel AT2 Receptor Agonist β-Pro7-AngIII Exerts Cardiac and Renal Anti-Fibrotic and Anti-Inflammatory Effects in High Salt-Fed Mice.International journal of molecular sciences · 2022Article
- The Angiotensin ATPharmacological reviews · 2022Review
- 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
- Intersection of stem cell biology and engineering towards next generationFrontiers in bioengineering and biotechnology · 2022Review
- Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting.Frontiers in endocrinology · 2022Review
- miR‑212 promotes renal interstitial fibrosis by inhibiting hypoxia‑inducible factor 1‑α inhibitor.Molecular medicine reports · 2021Article
- Angiotensin II type 1a receptor loss ameliorates chronic tubulointerstitial damage after renal ischemia reperfusion.Scientific reports · 2021Article
- Expression and Characterization of Relaxin Family Peptide Receptor 1 Variants.Frontiers in pharmacology · 2021Article
- The relaxin family peptide receptor 1 (RXFP1): An emerging player in human health and disease.Molecular genetics & genomic medicine · 2020Review
- Serelaxin and the ATACS pharmacology & translational science · 2020Article
- Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is a hallmark of chronic kidney disease, for which there is currently no effective cure. The hormone relaxin is emerging as an effective antifibrotic therapy; however, its mechanism of action is poorly understood. Recent studies have shown that relaxin disrupts the profibrotic actions of transforming growth factor-β1 (TGF-β1) by its cognate receptor, relaxin family peptide receptor 1 (RXFP1), extracellular signal-regulated kinase phosphorylation, and a neuronal nitric oxide synthase-dependent pathway to abrogate Smad2 phosphorylation. Since angiotensin II also inhibits TGF-β1 activity through its AT2 receptor (AT2R), we investigated the extent to which relaxin interacts with the AT2R. The effects of the AT2R antagonist, PD123319, on relaxin activity were examined in primary rat kidney myofibroblasts, and in kidney tissue from relaxin-treated male wild-type and AT2R-knockout mice subjected to unilateral ureteric obstruction. Relaxin's antifibrotic actions were significantly blocked by PD123319 in vitro and in vivo, or when relaxin was administered to AT2R-knockout mice. While heterodimer complexes were formed between RXFP1 and AT2Rs independent of ligand binding, relaxin did not directly bind to AT2Rs but signaled through RXFP1-AT2R heterodimers to induce its antifibrotic actions. These findings highlight a hitherto unrecognized interaction that may be targeted to control fibrosis progression.
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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.