ELABELA

The apelinergic system is a highly conserved pleiotropic system. It comprises the apelin receptor apelin peptide jejunum (APJ) and its two peptide ligands, Elabela/Toddler (ELA) and apelin, which have different spatiotemporal localizations. This system has been implicated in the regulation of the adipoinsular axis, in cardiovascular and central nervous systems, in carcinogenesis, and in pregnancy in humans. During pregnancy, the apelinergic system is essential for embryo cardiogenesis and vasculogenesis and for placental development and function...

INTRODUCTION: Proliferation, migration and invasion of extravillous trophoblasts (EVTs) play an important role in the progression of preeclampsia (PE). The purpose of this study was to investigate the molecular mechanism by which DNA methylase regulates the transcription level of APLNR and affects the phenotypic function of EVTs. MATERIALS AND METHODS: PE mice model and H/R model in HTR8/Svneo cells were constructed. Clinical samples of normal pregnant women and PE patients were collected...

Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice...

Heart failure is one of the most significant public health problems faced by millions of medical researchers worldwide. And pathological cardiac hypertrophy is considered one of the possible factors of increasing the risk of heart failure. Here, we introduce apelin/ELABELA-APJ system as a novel therapeutic target for cardiac hypertrophy, bringing about new directions in clinical treatment. Apelin has been proven to regulate cardiac hypertrophy through various pathways. And an increasing number of studies on ELABELA, the newly discovered endogenous ligand, suggest it can alleviate cardiac hypertrophy through mechanisms similar or different to apelin...

OBJECTIVE: Elabela is a newly discovered peptide hormone. This study aimed to determine the functional effects and mechanisms of action of elabela in rat pulmonary artery and trachea. MATERIALS AND METHODS: Vascular rings isolated from the pulmonary arteries of male Wistar Albino rats were placed in chambers in the isolated tissue bath system. The resting tension was set to 1g. After the equilibration period, the pulmonary artery rings were contracted with 10-6 M phenylephrine...

AIM: New therapeutic strategies are required to enhance the anticancer efficacy of chemotherapeutic drugs and to reduce their cytotoxicity. The purpose of this study was to assess the anti-tumor, antimetastatic and anti-apoptotic activities of sinapic acid (SA) and 3,3'-diindolylmethane (DIM) in solid Ehrlich carcinoma (SEC) induced in mice and combining SA or DIM compounds with cyclophosphamide (CYP). METHODS: For induction of solid tumor, the right hind limbs of mice were inoculated subcutaneously with Ehrlich carcinoma cells...

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INTRODUCTION: The apelin receptor binds two distinct endogenous peptides, apelin and ELA, which act in an autocrine/paracrine manner to regulate the human cardiovascular system. As a class A GPCR, targeting the apelin receptor is an attractive therapeutic strategy. With improvements in imaging techniques, and the stability and brightness of dyes, fluorescent ligands are becoming increasingly useful in studying protein targets. Here, we describe the design and validation of four novel fluorescent ligands; two based on [Pyr1]apelin-13 (apelin488 and apelin647), and two based on ELA-14 (ELA488 and ELA647)...

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 elabela-apelin/angiotensin domain type 1 receptor-associated protein (APJ) system is an important regulator in certain thrombosis-related diseases such as atherosclerosis, myocardial infarction, and cerebral infarction. Our previous reports have revealed that apelin exacerbates atherosclerotic lesions. However, the relationship between the elabela-apelin/APJ system and platelet aggregation and atherothrombosis is unclear. The results of the present study demonstrate that elabela and other endogenous ligands such as apelin-12, -17, and -36 induce platelet aggregation and thrombosis by activating the pannexin1(PANX1)-P2X7 signaling pathway...

We investigated the presence of asprosin (ASP), betatrophin, elabela (ELA), glucagon and subfatin (SUB) in the milk of mothers with gestational diabetes mellitus (GDM) and compared their levels with blood levels. We also investigated whether these peptides are synthesized by the breast. We investigated 12 volunteer mothers with GDM and 14 pregnant non-GDM control mothers. The peptides were measured using ELISA and their tissue localization was determined using immunohistochemistry. Breast milk contains ASP, betatrophin, ELA, glucagon and SUB...

Angiogenesis helps to improve neurological recovery by repairing damaged brain tissue and restoring cerebral blood flow (CBF). The role of the Elabela (ELA)-Apelin receptor (APJ) system in angiogenesis has gained much attention. We aimed to investigate the function of endothelial ELA on post-ischemic cerebral angiogenesis. Here, we demonstrated that the endothelial ELA expression was upregulated in the ischemic brain and treatment with ELA-32 mitigated brain injury and enhanced the restoration of CBF and newly formed functional vessels following cerebral ischemia/reperfusion (I/R) injury...

Mesoderm-derived cells, including bone, muscle, and mesenchymal stem/stromal cells (MSCs), constitute various parts of vertebrate body. Cell therapy with mesoderm specification in vitro may be a promising treatment for diseases affecting organs of mesodermal origin. Repair and regeneration of damaged organs with in vitro generation of mesoderm-derived tissues and MSCs hold a great potential for regenerative therapy. Therefore, understanding the signaling pathways involving mesoderm and mesoderm-derived cellular differentiation is important...

Ferroptosis is a form of non-apoptotic cell death caused by iron-dependent peroxidation of lipids. It contributes to ischemic stroke-induced neuronal damage. Elabela (ELA), a novel endogenous ligand for Apelin receptor (APJ), regulates oxidative stress and exerts a protective role in cardiovascular disease. However, the effect of ELA-APJ axis on cellular ferroptosis in cerebral ischemia/reperfusion (I/R) remains elusive. The present study showed that ELA and APJ were expressed on neurons and increased after cerebral I/R injury...

Elabela is a component of the apelinergic system and may exert a cardioprotective role by regulating the innate immune responses. Innate lymphoid cells (ILCs) have a significant role in initiating and progressing immune-inflammatory responses. While ILCs have been intensively investigated during the last decade, little is known about their relationship with the apelinergic system and their cardiac diversity in a gender-based paradigm. In this study, we investigated the polarization of cardiac ILCs by Elabela in males versus females in a mouse model...

The apelinergic system comprises two peptide ligands, apelin and ELABELA, and their cognate G-protein-coupled receptor, the apelin receptor APJ. Apelin is a peptide that was isolated from bovine stomach extracts; the distribution of the four main active forms, apelin-36, -17, -13, and pyr-apelin-13 differs between tissues. The mature form of ELABELA-32 can be transformed into forms called ELABELA-11 or -21. The biological function of the apelinergic system is multifaceted, and includes the regulation of angiogenesis, body fluid homeostasis, energy metabolism, and functioning of the cardiovascular, nervous, respiratory, digestive, and reproductive systems...

Preeclampsia is a leading contributor to increased maternal morbidity and mortality in the perinatal period. Increasing evidence demonstrates that ferroptosis is an essential mechanism for the pathogenesis of preeclampsia. Elabela is a novel small-molecule polypeptide, mainly expressed in embryonic and transplacental tissues, with an ability to promote cell proliferation and invasion. However, its specific regulatory mechanism in preeclampsia has not been completely elucidated. In this study, we first reveal an increased grade of ferroptosis accompanied by a downregulation of the expression of Elabela in preeclampsia placentas...

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...

Apelin and ELABELA (ELA), which are peptides belonging to the adipokines group, are endogenous peptide ligands of their receptor, APJ, which together constitute the apelinergic system. The apelinergic system is expressed in numerous human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. Apelin, being the most widely studied member of the apelinergic system, plays a key role in the cardiovascular system and exerts a pleiotropic effect in tissues...

Doxorubicin (DOX) is a chemotherapeutic drug for a variety of malignancies, while its application is restricted by the cardiovascular toxic effects characterized by oxidative stress. Ferroptosis is a novel iron-dependent regulated cell death driven by lipid peroxidation. Our study aimed to investigate the role of Elabela (ELA) in DOX-induced oxidative stress and ferroptosis. In cultured rat aortic adventitial fibroblasts (AFs), stimulation with DOX dramatically induced cytotoxicity with reduced cell viability and migration ability, and enhanced lactate dehydrogenase (LDH) activity...