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Cancers Sep 2022Apelin is a promising biomarker for the detection and prognosis of cancer. This review aims to synthesize current knowledge on associations of circulating apelin with... (Review)
Review
Apelin is a promising biomarker for the detection and prognosis of cancer. This review aims to synthesize current knowledge on associations of circulating apelin with cancer, illustrate knowledge gaps, and discuss future research. Following PRISMA guidelines, CINAHL, EMBASE, and PubMed were searched using terms "cancer AND apelin" between 2011 and 2021, full text, and English language. Inclusion criteria: measured circulating apelin in adults 18 years or older with cancer, and observational, cross-sectional, longitudinal, case-control, cohort, quasi-experimental, or randomized control trials. Excluded were studies with animal models, tissue samples only, secondary data analyses, systematic reviews, literature reviews, grey literature, and conference abstracts. 16 articles were included. There were significant variations in measurement methods between studies. Comparison of circulating apelin between cases and controls and associations of circulating apelin with clinicopathological characteristics were inconsistent. Variations in results suggest that the relationship between circulating apelin and cancer differs among cancer types. Differences in measurement methods between studies highlight the need for consistency in future research to draw meaningful conclusions. Future research should seek to standardize methods of detecting circulating apelin and examine its associations with specific cancer types to determine what role that circulating apelin may play in cancer development and progression.
PubMed: 36230579
DOI: 10.3390/cancers14194656 -
Clinica Chimica Acta; International... Dec 2019Apelin and its G protein-coupled receptor APJ are specifically expressed in endocrine organs. As well known, the hypothalamus is the regulatory center of endocrine... (Review)
Review
Apelin and its G protein-coupled receptor APJ are specifically expressed in endocrine organs. As well known, the hypothalamus is the regulatory center of endocrine activity, which combined with the pituitary and other gonads form regulatory axes involved in endocrine function. Evidence to date has shown that the apelin/APJ system plays an important role in mediating these axes, such as food intake, acute stress, steroid release, as well as, an anti-depressant-like activity. Here we review the effect of the apelin/APJ system on hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. Although the apelinergic system exerts a positive effect on these axes, there are contradictory reports on the role of apelin in endocrine disease caused by hypothalamic-pituitary disorders. Thus, as research continues to evolve we expect that apelin-related drugs can be used as a treatment for clinical diseases resulting from hypothalamic-pituitary dysfunction.
Topics: Animals; Apelin; Apelin Receptors; Humans; Hypothalamus; Pituitary Gland
PubMed: 31525345
DOI: 10.1016/j.cca.2019.09.011 -
Journal of Translational Medicine Nov 2023Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the...
BACKGROUND
Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia.
METHODS
RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults.
RESULTS
The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling.
CONCLUSION
We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.
Topics: Mice; Animals; Guinea Pigs; MicroRNAs; RNA, Long Noncoding; Apelin; Retinal Ganglion Cells; Gene Regulatory Networks; Biomarkers; Myopia
PubMed: 37932794
DOI: 10.1186/s12967-023-04662-x -
The Journal of Physiological Sciences :... Nov 2023Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and... (Review)
Review
Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and exerkines, such as apelin, adiponectin, leptin, irisin, and chemerin. Exercise and apelin increase thermogenesis and glucose uptake in pregnancy by activating AMPK, PI3K, PGC-1α, AKT1, UCP3, and sarcolipin. Exercise increases apelin levels to reduce preeclampsia symptoms by increasing eNOS, NO, placental growth factor (PlGF), and VEGF and decreasing levels of fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and oxidative stress. A negative relationship has been reported between plasma leptin and VOpeak/kg and VOpeak in women with gestational diabetes. In active women, decreases in leptin levels reduce the risk of preeclampsia by ~ 40%. Higher adiponectin levels are associated with greater physical activity and lead to increased insulin sensitivity. Increased adiponectin levels in preeclampsia and exercise counteract inflammatory and atherogenic activities while also having vascular protective effects. Exercise increases irisin levels that correlate negatively with fasting glucose, insulin concentration, and glycosylated hemoglobin levels. Irisin augments mRNA expression levels of UCP1 and cell death-inducing DNA fragmentation factor-like effector A (cidea) to cause browning of adipose tissue, increased thermogenesis, and increased energy consumption. Irisin concentrations in mothers with preeclampsia in the third trimester negatively correlate with systolic and diastolic blood pressure. Expression levels of chemerin, IL-6, and TNF-α are increased in gestational diabetes, and the increases in chemerin in late pregnancy positively correlate with the ratio of sFlt-1 to PlGF as a marker of preeclampsia. The effects of physical exercise on placentokines and exerkines in women at various stages of pregnancy remain poorly understood.
Topics: Pregnancy; Female; Humans; Placenta Growth Factor; Pre-Eclampsia; Pregnancy Proteins; Leptin; Apelin; Biomarkers; Diabetes, Gestational; Adiponectin; Fibronectins
PubMed: 37964253
DOI: 10.1186/s12576-023-00885-1 -
Journal of Cachexia, Sarcopenia and... Feb 2023Targeting of the apelin-apelin receptor (Apj) system may serve as a useful therapeutic intervention for the management of chronic kidney disease (CKD)-induced skeletal...
BACKGROUND
Targeting of the apelin-apelin receptor (Apj) system may serve as a useful therapeutic intervention for the management of chronic kidney disease (CKD)-induced skeletal muscle atrophy. We investigated the roles and efficacy of the apelin-Apj system in CKD-induced skeletal muscle atrophy.
METHODS
The 5/6-nephrectomized mice were used as CKD models. AST-120, a charcoal adsorbent of uraemic toxins (8 w/w% in diet), or apelin (1 μmol/kg) was administered to CKD mice to investigate the mechanism and therapeutic potential of apelin on CKD-induced skeletal muscle atrophy. The effect of indoxyl sulfate, a uraemic toxin, or apelin on skeletal muscle atrophy was evaluated using mouse myoblast cells (C2C12 cells) in vitro.
RESULTS
Skeletal muscle atrophy developed over time following nephrectomy at 12 weeks, as confirmed by a significant increase of atrogin-1 and myostatin mRNA expression in the gastrocnemius (GA) muscle and a decrease of lower limb skeletal muscle weight (P < 0.05, 0.01 and 0.05, respectively). Apelin expression in GA muscle was significantly decreased (P < 0.05) and elabela, another Apj endogenous ligand, tended to show a non-significant decrease at 12 weeks after nephrectomy. Administration of AST-120 inhibited the decline of muscle weight and increase of atrogin-1 and myostatin expression. Apelin and elabela expression was slightly improved by AST-120 administration but Apj expression was not, suggesting the involvement of uraemic toxins in endogenous Apj ligand expression. The administration of apelin at 1.0 μmol/kg for 4 weeks to CKD mice suppressed the increase of atrogin-1 and myostatin, increased apelin and Apj mRNA expression at 30 min after apelin administration and significantly ameliorated weight loss and a decrease of the cross-sectional area of hindlimb skeletal muscle.
CONCLUSIONS
This study demonstrated for the first time the association of the Apj endogenous ligand-uraemic toxin axis with skeletal muscle atrophy in CKD and the utility of therapeutic targeting of the apelin-Apj system.
Topics: Mice; Animals; Apelin; Myostatin; Ligands; Uremic Toxins; Muscle, Skeletal; Apelin Receptors; Muscular Atrophy; Renal Insufficiency, Chronic; RNA, Messenger
PubMed: 36562292
DOI: 10.1002/jcsm.13159 -
Gene Aug 2022Apelin is an endogenous ligand of the Apelin receptor (APLNR), a seven-transmembrane G protein-coupled receptor, which is widely distributed in human tissue. The... (Review)
Review
Apelin is an endogenous ligand of the Apelin receptor (APLNR), a seven-transmembrane G protein-coupled receptor, which is widely distributed in human tissue. The Apelin/APLNR system is involved in regulating several physiological and pathological processes. The Apelin expression is increased in a variety of cancer and the Apelin/APLNR system could regulate the development of tumors through mediating autophagy, apoptosis, pyroptosis, and other biological processes to regulate tumor cell proliferation, migration, and invasion. The Apelin/APLNR system also participates in immune response and immune regulation through PI3K-Akt, ERK-MAPK, and other signal pathways. The latest research points out that there is a negative regulatory relationship between APLNR and immune checkpoint PD-L1. In this review, we outline the significance of the Apelin/APLNR signaling pathway in tumorigenesis and its immune regulation. These endeavors provide new insights into the translational application of Apelin/APLNR in cancer and may contribute to the promotion of more effective treatments for cancers.
Topics: Apelin; Apelin Receptors; Humans; Immunity; Neoplasms; Phosphatidylinositol 3-Kinases; Tumor Microenvironment
PubMed: 35598689
DOI: 10.1016/j.gene.2022.146564 -
Frontiers in Endocrinology 2022The prevalence of maternal obesity during pregnancy is associated with the risk of gestational diabetes, preeclampsia, and cardiomyopathy. Environmental factors such as... (Review)
Review
The prevalence of maternal obesity during pregnancy is associated with the risk of gestational diabetes, preeclampsia, and cardiomyopathy. Environmental factors such as active lifestyles and apelin may lead to beneficial changes. In rats, apelin and exercise (45 to 65% VO for 6 to 9 weeks) during pregnancy increase brown adipose tissue (BAT) proteins such as Cidea, Elovl3, UCP1, PRDM16, and PGC-1α in males and females fetuses, while white adipose tissue (WAT) is reduced. In humans and animals, apelin and exercise stimulate the expression of the glucose transporters (GLUT1/2/4) in the muscle and adipose tissue through the PI3K/Akt and AMPK pathways. Hence, exercise and apelin may are known as regulators of energy metabolism and be anti-obesity and anti-diabetic properties. In mice, exercise also creates a short-term hypoxic environment in the pregnant mother, activating HIF-1, VEGF, and VEGFR, and increasing angiogenesis. Exercise and apelin also increase vasodilation, angiogenesis, and suppression of inflammation through the L-arginine/eNOS/NO pathway in humans. Exercise can stimulate the ACE2-Ang-(1-7)-Mas axis in parallel with inhibiting the ACE-Ang II-AT1 pathway. Exercise and apelin seem to prevent preeclampsia through these processes. In rats, moderate-intensity exercise (60 to 70% VO for 8 weeks) and apelin/APJ also may prevent pathological hypertrophy in pregnancy by activating the PI3K/Akt/mTOR/p70S6K pathway, PI3k-Akt-ERK1/2-p70S6K pathway, and the anti-inflammatory cytokine IL-10. Since pre-clinical studies have been more on animal models, future research with scientific guidelines should pay more attention to human specimens. In future research, time factors such as the first, second, and third trimesters of pregnancy and the intensity and duration of exercise are important variables that should be considered to determine the optimal intensity and duration of exercise.
Topics: Adipose Tissue, Brown; Animals; Apelin; Female; Humans; Male; Mice; Phosphatidylinositol 3-Kinases; Pre-Eclampsia; Pregnancy; Proto-Oncogene Proteins c-akt; Rats; Ribosomal Protein S6 Kinases, 70-kDa
PubMed: 36093083
DOI: 10.3389/fendo.2022.965167 -
Journal of Biochemistry Apr 2021The apelin (APJ) receptor was originally cloned as a gene encoding a putative G protein-coupled receptor related to angiotensin receptor type I. To date, two endogenous... (Review)
Review
The apelin (APJ) receptor was originally cloned as a gene encoding a putative G protein-coupled receptor related to angiotensin receptor type I. To date, two endogenous peptide ligands for APJ have been identified: apelin and elabela/Toddler. The apelin/APJ system regulates blood pressure and vascular tone. The endothelial and smooth muscle apelin/APJ systems exert opposite actions in the regulation of vascular tone. Binding of apelin to endothelial APJ promotes the release of vasodilators, such as nitric oxide and prostacyclin, leading to vasodilation. Alternatively, binding of apelin to smooth muscle APJ induces vasoconstriction, although the molecular mechanisms of the apelin-induced vasoconstriction are poorly understood. Recently, a critical role for interaction of APJ with α1-adrenergic receptor in the apelin-induced vasoconstriction was reported. The action of apelin on vascular tone may depend upon blood vessel type or pathological condition. Although the apelin/APJ system could serve as a potential therapeutic target for hypertension and cardiovascular disease, the role of this system in various cell types appears to be complicated.
Topics: Animals; Apelin; Apelin Receptors; Blood Pressure; Endothelial Cells; Humans; Hypertension; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Vasoconstriction
PubMed: 33169143
DOI: 10.1093/jb/mvaa129 -
Molecular Biology Reports Feb 2023Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the... (Review)
Review
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.
Topics: Humans; Apelin; Neurodegenerative Diseases; Apelin Receptors; Oxidative Stress; Brain Injuries; Receptors, G-Protein-Coupled
PubMed: 36378421
DOI: 10.1007/s11033-022-08075-9 -
Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical Reviews Feb 2023Apelin receptor (APJR) is a class A peptide (apelin) binding G protein-coupled receptor (GPCR) that plays a significant role in regulating blood pressure, cardiac... (Review)
Review
Apelin receptor (APJR) is a class A peptide (apelin) binding G protein-coupled receptor (GPCR) that plays a significant role in regulating blood pressure, cardiac output, and maintenance of fluid homeostasis. It is activated by a wide range of endogenous peptide isoforms of apelin and elabela. The apelin peptide isoforms contain distinct structural features that aid in ligand recognition and activation of the receptor. Site-directed mutagenesis and structure-based studies have revealed the involvement of extracellular and transmembrane regions of the receptor in binding to the peptide isoforms. The structural features of APJR activation of the receptor as well as mediating G-protein and β-arrestin-mediated signaling are delineated by multiple mutagenesis studies. There is increasing evidence that the structural requirements of APJR to activate G-proteins and β-arrestins are different, leading to biased signaling. APJR also responds to mechanical stimuli in a ligand-independent manner. A multitude of studies has focused on developing both peptide and non-peptide agonists and antagonists specific to APJR. Apelin/elabela-activated APJR orchestrates major signaling pathways such as extracellular signal-regulated kinase (ERKs), protein kinase B (PKB/Akt), and p70S. This review focuses on the structural and functional characteristics of apelin, elabela, APJR, and their interactions involved in the binding and activation of the downstream signaling cascade. We also focus on the diverse signaling profile of APJR and its ligands and their involvement in various physiological systems.
PubMed: 36919024
DOI: 10.1007/s12551-023-01044-x