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Relaxin

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https://www.readbyqxmd.com/read/28646638/corrigendum-to-oncolytic-adenovirus-expressing-relaxin-ydc002-enhances-therapeutic-efficacy-of-gemcitabine-against-pancreatic-cancer-cancer-lett-396-2017-155-166
#1
Kyung Hee Jung, Il-Kyu Choi, Hee-Seung Lee, Hong Hua Yan, Mi Kwon Son, Hyo Min Ahn, JinWoo Hong, Chae-Ok Yun, Soon-Sun Hong
No abstract text is available yet for this article.
June 21, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28634453/relaxin-family-peptide-receptors-1-and-2-are-fully-functional-in-the-bovine
#2
Yanzhenzi Dai, Richard Ivell, Xuan Liu, Dana Janowski, Ravinder Anand-Ivell
In most mammals the peptide hormone relaxin is a key physiological component regulating early pregnancy and birth. However, synteny analysis shows that the gene encoding ovarian relaxin-2 is deleted in cows and sheep. While, these ruminants appear to exhibit a relaxin-like physiology, as in other mammals, until now a molecular understanding of this has been lacking. Cloning and expression analysis of the cognate bovine receptor for relaxin, RXFP1, as well as of the structurally related receptor, RXFP2, in female tissues, shows that these are expressed in a similar way to other mammals...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28634079/relaxin-reduces-susceptibility-to-post-infarct-atrial-fibrillation-in-mice-due-to-anti-fibrotic-and-anti-inflammatory-properties
#3
Thomas Beiert, Vedat Tiyerili, Vincent Knappe, Verena Effelsberg, Markus Linhart, Florian Stöckigt, Sabine Klein, Robert Schierwagen, Jonel Trebicka, Georg Nickenig, Jan W Schrickel, René P Andrié
BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28631012/rapid-preparation-of-bioluminescent-tracers-for-relaxin-family-peptides-using-sortase-catalysed-ligation
#4
Jia-Hui Wang, Xiao-Xia Shao, Meng-Jun Hu, Dian Wei, Wei-Han Nie, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family is a group of peptide hormones with a variety of biological functions by activating G protein-coupled receptors RXFP1-4. We recently developed bioluminescent tracers for their receptor-binding assays by chemical conjugation with the ultrasensitive NanoLuc reporter. To simplify preparation of the bioluminescent tracers, in the present study, we established a sortase-catalysed ligation approach using the chimeric R3/I5 as a model. Following catalysis by recombinant sortase A, a NanoLuc reporter carrying the LPETG sortase recognition motif at the C-terminus was efficiently ligated to an R3/I5 peptide carrying four successive Gly residues at the A-chain N-terminus, via the formation of a peptide bond between the C-terminal LPET sequence of NanoLuc and the A-chain N-terminal Gly residue of R3/I5...
June 19, 2017: Amino Acids
https://www.readbyqxmd.com/read/28621254/use-of-microcomputed-tomography-to-measure-the-relaxin-induced-expansion-of-intrapubic-ligaments-in-mice
#5
Heather A Zimmerman, Richard P Kennan, Chunlian Zhang, Kashmira Shah, Douglas G Johns, Joseph J Lynch, Maya Dajee
Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that μCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points...
June 15, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28620300/novel-anti-fibrotic-therapies
#6
REVIEW
Benita L McVicker, Robert G Bennett
Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Novel treatments have recently been identified that hold promise as potential therapeutic agents for cardiovascular diseases associated with fibrosis, as well as other fibrotic conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28613403/opposite-actions-of-urotensin-ii-and-relaxin-2-on-cellular-expression-of-fibronectin-in-renal-fibrosis-a-preliminary-experimental-study
#7
Valeria Cernaro, Maria Antonietta Medici, Federica Bianco, Domenico Santoro, Antonio Lacquaniti, Adolfo Romeo, Silvia Lucisano, Antoine Buemi, Michele Buemi
Our aim was to evaluate the role of urotensin II, urantide (urotensin II receptor antagonist) and relaxin-2 on the cellular expression of fibronectin as a surrogate marker for renal fibrosis. We employed LLC-PK1 renal tubular epithelial cells and assessed the influence on the fibrotic process of the above-mentioned substances by using anti-fibronectin antibodies in western blot analysis. The addition of urotensin II increased fibronectin expression. Urantide reduced the positivity for fibronectin caused by urotensin II (P<0...
June 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28607406/distinct-activation-modes-of-the-relaxin-family-peptide-receptor-2-in-response-to-insulin-like-peptide-3-and-relaxin
#8
Shoni Bruell, Ashish Sethi, Nicholas Smith, Daniel J Scott, Mohammed Akhter Hossain, Qing-Ping Wu, Zhan-Yun Guo, Emma J Petrie, Paul R Gooley, Ross A D Bathgate
Relaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It is structurally related to the human relaxin receptor RXFP1 and can be activated by human gene-2 (H2) relaxin as well as its cognate ligand insulin-like peptide 3 (INSL3). Both receptors possess an N-terminal low-density lipoprotein type a (LDLa) module that is necessary for activation and is joined to a leucine-rich repeat domain by a linker. This linker has been shown to be important for H2 relaxin binding and activation of RXFP1 and herein we investigate the role of the equivalent region of RXFP2...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607363/development-of-a-selective-agonist-for-relaxin-family-peptide-receptor-3
#9
Dian Wei, Meng-Jun Hu, Xiao-Xia Shao, Jia-Hui Wang, Wei-Han Nie, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely RXFP1-4. Among these receptors, RXFP3 lacks a specific natural or synthetic agonist at present. A previously designed chimeric R3/I5 peptide, consisting of the B-chain of relaxin-3 and the A-chain of INSL5, displays equal activity towards the homologous RXFP3 and RXFP4. To increase its selectivity towards RXFP3, in the present study we conducted extensive mutagenesis around the B-chain C-terminal region of R3/I5...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606038/site-related-effects-of-relaxin-in-the-gastrointestinal-tract-through-nitric-oxide-signaling-an-updated-report
#10
Rachele Garella, Roberta Squecco, Maria Caterina Baccari
The peptide hormone relaxin (RLX), in addition to its effects on reproduction, has been reported to influence gastrointestinal motility. Interestingly, the digestive tract has been shown to express RLX receptors and the hormone appears to exert site-specific effects acting at the neural or at the smooth muscle level, mainly by a nitric oxide (NO)-mediated mechanism. NO, released by the enteric nerves and/or smooth muscle cells, is one of the main mediators of gastrointestinal relaxation. In fact, in murine in vitro preparations, RLX depresses organ motility acting at the neural level in the stomach and at the muscular level in the small intestine; conversely, in the colon, this hormone paradoxically increases contractility operating at both neural and muscle levels...
June 12, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28592882/ml290-is-a-biased-allosteric-agonist-at-the-relaxin-receptor-rxfp1
#11
Martina Kocan, Mohsin Sarwar, Sheng Y Ang, Jingbo Xiao, Juan J Marugan, Mohammed A Hossain, Chao Wang, Dana S Hutchinson, Chrishan S Samuel, Alexander I Agoulnik, Ross A D Bathgate, Roger J Summers
Activation of the relaxin receptor RXFP1 has been associated with improved survival in acute heart failure. ML290 is a small molecule RXFP1 agonist with simple structure, long half-life and high stability. Here we demonstrate that ML290 is a biased agonist in human cells expressing RXFP1 with long-term beneficial actions on markers of fibrosis in human cardiac fibroblasts (HCFs). ML290 did not directly compete with orthosteric relaxin binding and did not affect binding kinetics, but did increase binding to RXFP1...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580623/the-relationship-of-circulating-relaxin-2-concentrations-with-short-term-prognosis-in-patients-with-acute-heart-failure-the-relahf-study
#12
Pablo Herrero-Puente, Belén Prieto-García, María García-García, Pere Llorens, Francisco Javier Martín-Sánchez, Javier Jacob, Alexandre Mebazaa, Christian Mueller, Alan S Maisel, Víctor Gil, Pablo García-Hernandez, Òscar Miró
AIMS: This study aimed to determine the frequency of detectable relaxin-2 concentrations and associated factors in patients with acute heart failure (AHF) and to establish relationships with short-term outcome and clinical and analytical parameters. METHODS AND RESULTS: We performed a prospective, analytical, observational, multicentre study with cohort follow-up. We collected sociodemographic variables, previous history, basal status, previous treatment, vital signs, electrocardiographic and analytical data in the emergency department...
June 5, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28552862/imbalanced-angiogenesis-in-peripartum-cardiomyopathy%C3%A3-diagnostic-value-of-placenta-growth-factor
#13
Alexandre Mebazaa, Marie-France Seronde, Etienne Gayat, Kemi Tibazarwa, Dilly O C Anumba, Najla Akrout, Malha Sadoune, Jamela Sarb, Mattia Arrigo, Justina Motiejunaite, Said Laribi, Matthieu Legrand, Lydia Deschamps, Loubina Fazal, Lila Bouadma, Corinne Collet, Philippe Manivet, Alain Cohen Solal, Jean-Marie Launay, Jane-Lise Samuel, Karen Sliwa
BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65)...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28540295/relaxin-attenuates-contrast-induced-human-proximal-tubular-epithelial-cell-apoptosis-by-activation-of-the-pi3k-akt-signaling-pathway-in-vitro
#14
Xiang-Cheng Xie, Yizhi Cao, Xiu Yang, Qun-Hong Xu, Wei Wei, Ming Wang
Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms. Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28487955/regulation-of-mrna-gene-expression-of-members-of-the-nf-%C3%AE%C2%BAb-transcription-factor-gene-family-by-angiotensin-ii-and-relaxin-2-in-normal-and-cancer-prostate-cell-lines
#15
Kamila Domińska, Karolina Kowalska, Zuzanna Elżbieta Matysiak, Elżbieta Płuciennik, Tomasz Ochędalski, Agnieszka Wanda Piastowska-Ciesielska
An increasing number of researchers are focusing on the influence of local peptide hormones such as angiotensin II (Ang II) and relaxin 2 (RLN2) in the regulation of inflammation and carcinogenesis. The interaction between the renin‑angiotensin system (RAS) and relaxin family peptide system (RFPS) is known to influence the proliferation, adhesion and migration of normal and cancer prostate cell lines. The aim of the present study was to evaluate changes in the expression of nuclear factor‑κB subunit 1 (NFKB1), nuclear factor‑κB subunit 2 (NFKB2), REL proto‑oncogene nuclear factor‑κB p65 subunit (REL), RELA proto‑oncogene nuclear factor‑κB subunit (RELA) and RELB proto‑oncogene nuclear factor‑κB subunit (RELB) mRNA caused by Ang II and RLN2...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482627/improvement-of-pulmonary-arterial-compliance-and-further-pulmonary-hemodynamic-effects-of-serelaxin-in%C3%A2-a%C3%A2-sheep-model
#16
René Schiffner, Juliane Reiche, Martin Schmidt, Christian Jung, Sebastian Walther, Andrey Irintchev, Sabine J Bischoff
BACKGROUND: The influence of the recombinant form of human relaxin-2 (serelaxin) on pulmonary hemodynamics under physiologic conditions have not been the subject of studies in an animal model up until now. METHODS: We therefore utilised the large animal model sheep, convenient in its similar cardiovascular physiology, to investigate said influence. All animals underwent right heart catheterization, a safe and reliable invasive procedure for the assessment of pulmonary hemodynamics, and then received either 30μg/kg serelaxin (n = 11) or saline (n = 13)...
May 2, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28468839/human-relaxins-rlnh1-rlnh2-their-receptor-rxfp1-and-fetoplacental-growth
#17
Kelly Yamasato, Pai-Jong Stacy Tsai, James Davis, Sandra Yamamoto, Gillian Bryant-Greenwood
Relaxin, a systemic and placental hormone, has potential roles in fetoplacental growth. Human placenta expresses two RLN genes, RLNH1 and RLNH2. Maternal obesity is common and is associated with abnormal fetal growth. Our aims were to relate systemic and cord blood RLNH2, placental RLNs and their receptor (RXFP1) with fetoplacental growth in context of maternal body mass index, and associations with insulin-like growth factor 2 (IGF2) and vascular endothelial growth factor A (VEGFA) in the same placentas. Systemic, cord blood and placental samples were collected prior to term labor, divided by prepregnancy body mass index: underweight/normal (N=25) and overweight/obese (N=44)...
May 3, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28467988/liver-fibrosis-understanding-the-dynamics-of-bidirectional-wound-repair-to-inform-the-design-of-markers-and-therapies
#18
John P Iredale, Antonella Pellicoro, Jonathan A Fallowfield
BACKGROUND: Liver fibrosis is the final common pathway of iterative or chronic liver damage. When it reaches an advanced stage, cirrhosis develops and this indicates a loss of normal liver architecture, disruption of normal blood flow, the development of nodules of proliferative hepatocytes and consequent functional failure. Cirrhosis is also associated with life-threatening complications. Importantly, this dysregulation of blood flow involves changes resulting from both architectural disruption and a dynamic rise in portal pressure mediated in part by the contraction of myofibroblasts - the major cell mediator of the fibrogenic process - which are derived from hepatic stellate cells (HSC) and termed activated HSC (myofibroblast/activated HSC)...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28466571/synthesis-of-relaxin-2-and-insulin-like-peptide-5-enabled-by-novel-tethering-and-traceless-chemical-excision
#19
Kishore Thalluri, Binbin Kou, Xu Yang, Alexander N Zaykov, John P Mayer, Vasily M Gelfanov, Fa Liu, Richard D DiMarchi
This report presents an entirely chemical, general strategy for the synthesis of relaxin-2 and insulin-like peptide 5. Historically, these two peptides have represented two of the more synthetically challenging members of the insulin superfamily. The key synthetic steps involve two sequential oxime ligations to covalently link the individual A-chain and B-chain, followed by disulfide bond formation under aqueous, redox conditions. This is followed by two chemical reactions that employ diketopiperazine cyclization-mediated cleavage and ester hydrolysis to liberate the connecting peptide and the heterodimeric product...
May 3, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28453739/relaxin-reproductive-safeguard-turned-cardiac
#20
Stefan Janssens
No abstract text is available yet for this article.
May 1, 2017: Cardiovascular Research
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