ArticleThe Journal of biological chemistry2015
Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- TAZ WW Domain-Mediated Regulation of Gluconeogenesis and Tumorigenesis in Hepatocellular Carcinoma through Interaction with the Glucocorticoid Receptor.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Polystyrene nanoplastics and benzo(a)pyrene synergistically induce lung fibrosis and inflammation via relaxin signalling in mice.Communications biology · 2026Article
- Nutritional and hormonal regulation of mitochondrial biogenesis drives fat body remodeling for reproductive competence.Journal of advanced research · 2026Article
- Role of the PKA-PGC1α-BACE1 Signaling Pathway in Aluminum-Induced Neurotoxicity in PC12 Cells.ACS omega · 2025Article
- The role of relaxins in blood cell modulation: interactions with relaxin family peptide receptor 1 (RXFP1) and glucocorticoid receptor (GR).Clinical science (London, England : 1979) · 2025Review
- Intergenerational effects of early life protein restriction on adipose tissue development as revealed by sheep transcriptomic analyses.Scientific reports · 2025Article
- A fibrin gel-loaded Gouqi-derived nanovesicle (GqDNV) repairs the heart after myocardial infarction by inhibiting p38 MAPK/NF-κB p65 pathway.Journal of nanobiotechnology · 2025Article
- Relaxin-2 Exhibits a Beneficial Role in Energy Metabolism to Alleviate Atrial Fibrillation Susceptibility.ACS pharmacology & translational science · 2025Article
- Transcriptomic analysis identifies enrichment of cAMP/PKA/CREB signaling in invasive lobular breast cancer.Breast cancer research : BCR · 2024Article
- LncRNA MALAT1 and Ischemic Stroke: Pathogenesis and Opportunities.Molecular neurobiology · 2024Review
- Significance of plasma relaxin-2 levels in patients with primary hypertension and type 2 diabetes mellitus.Wiener medizinische Wochenschrift (1946) · 2024Article
- 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
- Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways.Molecular metabolism · 2022Article
- Secretory products of the corpus luteum and preeclampsia.Human reproduction update · 2021Review
- Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis.Nature nanotechnology · 2021Article
- Crtc1 Deficiency Causes Obesity Potentially via Regulating PPARγ Pathway in White Adipose.Frontiers in cell and developmental biology · 2021Article
- FOXO1 inhibition prevents renal ischemia-reperfusion injury via cAMP-response element binding protein/PPAR-γ coactivator-1α-mediated mitochondrial biogenesis.British journal of pharmacology · 2020Article
- Relaxin reduces endothelium-derived vasoconstriction in hypertension: Revealing new therapeutic insights.British journal of pharmacology · 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
- Human relaxin-2 attenuates hepatic steatosis and fibrosis in mice with non-alcoholic fatty liver disease.Laboratory investigation; a journal of technical methods and pathology · 2019Article
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3 authors at 2 institutions in 1 country.
Funding
Abstract
Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin.
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