Oxytocin Signaling Pathway: From Cell Biology to Clinical Implications

Iovino, Michele; Messana, Tullio; Tortora, Anna; Giusti, Consuelo; Lisco, Giuseppe; Giagulli, Vito Angelo; Guastamacchia, Edoardo; Pergola, Giovanni De; Triggiani, Vincenzo

doi:10.2174/1871530320666200520093730

Cited by 21 publications

(31 citation statements)

References 252 publications

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“…In mammals, the two peptides have four cognate receptor subtypes encoded by four distinct genes: AVPR1A, AVPR1B, AVPR2 and OXTR. The actions of OT are mediated by the OT receptor (OTR) and include both behavioral and gonadal regulation and, in mammals, the powerful contractions of the uterus as well as stimulation of milk ejection (6). The responses to VT are triggered in mammals by three distinct receptor subtypes (7) and are more complex [see (8), for review].…”

Section: Introductionmentioning

confidence: 99%

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

2022

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The neuronal and neuroendocrine peptides oxytocin (OT) and vasotocin (VT), including vasopressins, have six cognate receptors encoded by six receptor subtype genes in jawed vertebrates. The peptides elicit a broad range of responses that are specifically mediated by the receptor subtypes including neuronal functions regulating behavior and hormonal actions on reproduction and water/electrolyte balance. Previously, we have demonstrated that these six receptor subtype genes, which we designated VTR1A, VTR1B, OTR, VTR2A, VTR2B and VTR2C, arose from a syntenic ancestral gene pair, one VTR1/OTR ancestor and one VTR2 ancestor, through the early vertebrate whole-genome duplications (WGD) called 1R and 2R. This was supported by both phylogenetic and chromosomal conserved synteny data. More recently, other studies have focused on confounding factors, such as the OTR/VTR orthologs in cyclostomes, to question this scenario for the origin of the OTR/VTR gene family; proposing instead less parsimonious interpretations involving only one WGD followed by complex series of chromosomal or segmental duplications. Here, we have updated the phylogeny of the OTR/VTR gene family, including a larger number of vertebrate species, and revisited seven representative neighboring gene families from our previous conserved synteny analyses, adding chromosomal information from newer high-coverage genome assemblies from species that occupy key phylogenetic positions: the polypteriform fish reedfish (Erpetoichthys calabaricus), the cartilaginous fish thorny skate (Amblyraja radiata) and a more recent high-quality assembly of the Western clawed frog (Xenopus tropicalis) genome. Our analyses once again add strong support for four-fold symmetry, i.e., chromosome quadruplication in the same time window as the WGD events early in vertebrate evolution, prior to the jawed vertebrate radiation. Thus, the evolution of the OTR/VTR gene family can be most parsimoniously explained by two WGD events giving rise to the six ancestral genes, followed by differential gene losses of VTR2 genes in different lineages. We also argue for more coherence and clarity in the nomenclature of OT/VT receptors, based on the most parsimonious scenario.

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Section: Introductionmentioning

confidence: 99%

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

2022

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“…Recent evidence indicates that perturbations of the thyroid hormone signaling pathway and antibodies are associated with GDM development and mal-outcome [ 49 , 51 ]. Emerging evidence suggests a role of OT in the pathogenesis of insulin resistance, obesity, and dyslipidemia [ 52 , 53 ], which are hallmarks or risk factors for GDM. A significant weight loss and improvement of insulin sensitivity, pancreatic β-cell responsivity, and lipid metabolism can be observed in rodents, nonhuman primates, and humans after chronic subcutaneous or intranasal OT treatment [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Biological networks in gestational diabetes mellitus: insights into the mechanism of crosstalk between long non-coding RNA and N6-methyladenine modification

Bai

2022

BMC Pregnancy Childbirth

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Background Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. The mechanism underlying the crosstalk between long non-coding RNAs (lncRNAs) and N6-methyladenine (m6A) modification in GDM remain unclear. Methods We generated a lncRNA-mediated competitive endogenous RNA (ceRNA) network using comprehensive data from the Gene Expression Omnibus database, published data, and our preliminary findings. m6A-related lncRNAs were identified based on Pearson correlation coefficient (PCC) analysis using our previous profiles. An integrated pipeline was established to constructed a m6A-related subnetwork thereby predicting the potential effects of the m6A-related lncRNAs. Results The ceRNA network was composed of 16 lncRNAs, 17 microRNAs, 184 mRNAs, and 338 edges. Analysis with the Kyoto Encyclopedia of Genes and Genomes database demonstrated that genes in the ceRNA network were primarily involved in the development and adverse outcomes of GDM, such as those in the fatty acid-metabolism pathway, the peroxisome proliferator-activated receptor signaling pathway, and thyroid hormone signaling pathway. Four m6A-related lncRNAs were involved in the ceRNA network, including LINC00667, LINC01087, AP000350.6, and CARMN. The m6A-related subnetwork was generated based on these four lncRNAs, their ceRNAs, and their related m6A regulators. Genes in the subnetwork were enriched in certain GDM-associated hormone (thyroid hormone and oxytocin) signaling pathways. LINC00667 was positively correlated with an m6A “reader” (YTHDF3; PCC = 0.95) and exhibited the highest node degree in the ceRNA network. RIP assays showed that YTHDF3 directly bind LINC00667. We further found that MYC possessed the highest node degree in a protein–protein interaction network and competed with LINC00667 for miR-33a-5p. qPCR analysis indicated that LINC00667, YTHDF3 and MYC levels were upregulated in the GDM placentas, while miR-33a-5p was downregulated. In a support-vector machine classifier, an m6A-related module composed of LINC00667, YTHDF3, MYC, and miR-33a-5p showed excellent classifying power for GDM in both the training and the testing dataset, with an accuracy of 76.19 and 71.43%, respectively. Conclusions Our results shed insights into the potential role of m6A-related lncRNAs in GDM and have implications in terms of novel therapeutic targets for GDM.

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“…Collectively, Rh and AZ enriched 5 new pathways after their combined use. Among them, the oxytocin signaling pathway is related to the cardiovascular system (36,37). Oxytocin could reduce the force and rate of heart contraction and increase vasodilatation by mediating the atrial natriuretic peptide-Cyclic GMP (ANP-cGMP), and Nitric oxide-Cyclic GMP (NO-cGMP) pathways (38)(39)(40), which may reduce symptoms such as pulmonary hypertension or hypertension caused by AS (41).…”

Section: Discussionmentioning

confidence: 99%

The combined use of acetazolamide and Rhodiola in the prevention and treatment of altitude sickness

Cao¹,

Zhang²,

Huang³

et al. 2022

Ann Transl Med

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Background: Altitude sickness (AS), which is caused by rapid exposure to low amounts of oxygen at high elevations, poses a great threat to humans working and traveling in these conditions. Acute mountain sickness includes high-altitude pulmonary edema and high-altitude cerebral edema. Acetazolamide (AZ) is often used to treat pulmonary edema caused by hypoxia. Additionally, the medicinal plant Rhodiola rosea L. (Rh) is often used to prevent AS in the Qinghai-Tibet plateau. However, the mechanisms of action of Rh and AZ in the treatment of AS remain unclear. To date, no research has been conducted to determine whether their combined use has better efficacy in the treatment and prevention of AS than their separate use.Methods: We used the method of network pharmacology to analyze the mechanisms of Rh and AZ in combination in the prevention and treatment of AS, and also verified our results. Results:The hypoxia-inducible factor (HIF)-1 signaling pathway, which is related to hypoxia, and other pathways related to pulmonary hypertension, became more enriched after the combined use of the 2 drugs.Additionally, Rh and AZ regulated most nodes in the AS network. Further, compared to their separate use, the combined use of Rh and AZ further downregulated the gene expression of HIF-1α and improved hemodynamics in rats, and thus helped the body to reduce its sensitivity to hypoxic environments and pulmonary artery pressure.Conclusions: This study provides evidence supporting the combined use of AZ and Rh in the treatment of AS.

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Oxytocin Signaling Pathway: From Cell Biology to Clinical Implications

Cited by 21 publications

References 252 publications

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

The Evolution of Oxytocin and Vasotocin Receptor Genes in Jawed Vertebrates: A Clear Case for Gene Duplications Through Ancestral Whole-Genome Duplications

Biological networks in gestational diabetes mellitus: insights into the mechanism of crosstalk between long non-coding RNA and N6-methyladenine modification

The combined use of acetazolamide and Rhodiola in the prevention and treatment of altitude sickness

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