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Yuanyuan Liu, Liquan Wang, Hongjun Shi
Pre-eclampsia (PE) is a pregnancy-specific syndrome that is characterized by hypertension and proteinuria. The etiology of PE is not completely understood but is believed to involve placental insufficiency and maternal vascular damage. Growing evidence supports an important role for the apelin receptor (APJ) system in regulating cardiovascular physiology. There are two vertebrate APJ ligands, APELIN and ELABELA, both of which mediate vasodilatory functions. A recent study linked deficient ELABELA signaling and the development of PE, though the molecular mechanism remains largely unknown...
January 9, 2019: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Z Meng, S Zhou, N C Hong
No abstract text is available yet for this article.
December 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
John Canfield, Sefa Arlier, Ezinne F Mong, John Lockhart, Jeffrey VanWye, Ozlem Guzeloglu-Kayisli, Frederick Schatz, Ronald R Magness, Charles J Lockwood, John C M Tsibris, Umit A Kayisli, Hana Totary-Jain
Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role of LIN28A and LIN28B in modulating cell metabolism, differentiation, and invasion, we hypothesized that LIN28A and/or LIN28B regulates trophoblast differentiation and invasion, and that its dysregulation may contribute to PE. Here we show that LIN28B is expressed ∼1300-fold higher than LIN28A in human term placenta and is the predominant paralog expressed in primary human trophoblast cultures...
October 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yixian Zhang, Yonggang Wang, Yan Lou, Manyu Luo, Yue Lu, Zhuo Li, Yangwei Wang, Lining Miao
The Apelin/APJ system is involved in a wide range of biological functions. For a long time, Apelin was thought to be the only ligand for APJ. Recently, a new peptide that acts via APJ and has similar functions, called Elabela, was identified. Elabela has beneficial effects on body fluid homeostasis, cardiovascular health, and renal insufficiency, as well as potential benefits for metabolism and diabetes. In this review, the properties and biological functions of this new peptide are discussed in comparison with those of Apelin...
September 26, 2018: Peptides
Hong Zhang, Dawei Gong, Liqiang Ni, Lin Shi, Wendong Xu, Min Shi, Juan Chen, Yong Ai, Xiangcheng Zhang
BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D)...
2018: Cellular Physiology and Biochemistry
Bogdan Panaitescu, Roberto Romero, Nardhy Gomez-Lopez, Percy Pacora, Offer Erez, Felipe Vadillo-Ortega, Lami Yeo, Sonia S Hassan, Chaur-Dong Hsu
OBJECTIVE: ELABELA is a newly discovered peptide hormone that appears to be implicated in the mechanisms leading to preeclampsia, independently of angiogenic factors. The aim of the current study was to investigate whether women with early- or late-onset preeclampsia have altered ELABELA plasma concentrations compared to gestational-age-matched normal pregnant women. METHODS: This retrospective cross-sectional study focused on the maternal plasma samples collected from 232 women with a singleton pregnancy who were allocated into the following groups: (1) early-onset preeclampsia (<34 weeks of gestation, N = 56); (2) late-onset preeclampsia (≥34 weeks of gestation, N = 57); and (3) gestational-age-matched controls with a normal pregnancy [(<34 weeks of gestation, N = 59); (≥34 weeks of gestation, N = 60)]...
July 22, 2018: Journal of Maternal-fetal & Neonatal Medicine
Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Sungsam Gong, Justyna Dopierala, Gordon C S Smith, D Stephen Charnock-Jones, Stephen Tong
The genetic deletion of apelin receptor early endogenous ligand (Elabela; official name APELA) produces a preeclampsia-like phenotype in mice. However, evidence linking ELABELA with human disease is lacking. Therefore, we measured placental mRNA and circulating ELABELA in human samples. ELABELA mRNA (measured by RNA sequencing) was unchanged in 82 preeclamptic placentas compared with 82 matched controls (mean difference, 0.53%; 95% CI, -25.9 to 27.0; P = 0.78). We measured circulating ELABELA in 32 women with preterm preeclampsia (delivered at <34 weeks' gestation) and 32 matched controls sampled at the same gestational age...
August 2018: American Journal of Pathology
Gokhan Artas, Sait Ozturk, Tuncay Kuloglu, Adile Ferda Dagli, Murat Gonen, Hakan Artas, Suleyman Aydin, Fatih Serhat Erol
AIM: This study aimed to investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. MATERIAL AND METHODS: We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4-6-µm-thick sections obtained from paraffin blocks...
April 6, 2018: Turkish Neurosurgery
Keiji Kuba, Teruki Sato, Yumiko Imai, Tomokazu Yamaguchi
Apelin is an endogenous peptide ligand for the G protein-coupled receptor APJ/AGTRL1/APLNR and is widely expressed throughout human body. In adult hearts Apelin-APJ/Apelin receptor axis is potently inotropic, vasodilatory, and pro-angiogenic and thereby contributes to maintaining homeostasis in normal and pathological hearts. Apelin-APJ/Apelin receptor is also involved in heart development including endoderm differentiation, heart morphogenesis, and coronary vascular formation. APJ/Apelin receptor had been originally identified as an orphan receptor for its sequence similarity to Angiotensin II type 1 receptor, and it was later deorphanized by identification of Apelin in 1998...
April 21, 2018: Peptides
Zhi Wang, Jin Huang, Daozhan Yu, Dawei Gong
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Kyungsoo Shin, Calem Kenward, Jan K Rainey
Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein-coupled receptor named the apelin receptor (AR/APJ/APLNR). Ligand-AR interactions have been implicated in regulation of the adipoinsular axis, cardiovascular system, and central nervous system alongside pathological processes. Each ligand may be processed into a variety of bioactive isoforms endogenously, with apelin ranging from 13 to 55 amino acids and apela from 11 to 32, typically being cleaved C-terminal to dibasic proprotein convertase cleavage sites...
December 12, 2017: Comprehensive Physiology
Jin Xu, Linxi Chen, Zhisheng Jiang, Lanfang Li
The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis, and energy metabolism regulation. Recently, a new endogenous peptidic ligand of APJ, named Elabela, has been identified and shown to play a crucial role in embryonic development. In addition, increasing evidences show that Elabela is also intimate associated with a large number of physiological processes in adulthood...
September 2018: Journal of Cellular Physiology
Qionglin Zhou, Kai Zhang, Yu Guo, Linxi Chen, Lanfang Li
No abstract text is available yet for this article.
March 1, 2018: Acta Biochimica et Biophysica Sinica
Megan L Norris, Andrea Pauli, James A Gagnon, Nathan D Lord, Katherine W Rogers, Christian Mosimann, Leonard I Zon, Alexander F Schier
Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The 'specification model' postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the 'migration model' posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration...
November 9, 2017: ELife
Lanfang Li, Qionglin Zhou, Xiaoxiao Li, Linxi Chen
No abstract text is available yet for this article.
November 1, 2017: Acta Biochimica et Biophysica Sinica
Irinna Papangeli, Hyung J Chun
Elabela (ELA), the second peptide ligand for the apelin receptor, APLNR, was previously found in lower vertebrates to be crucial for endoderm and cardiac development. Two new studies report on the phenotypes of Ela null mice, ranging from defective embryogenesis to preeclampsia, providing new insights and raising greater intrigue on this cardiometabolic pathway.
November 2017: Trends in Endocrinology and Metabolism: TEM
Bikram Sharma, Lena Ho, Gretchen Hazel Ford, Heidi I Chen, Andrew B Goldstone, Y Joseph Woo, Thomas Quertermous, Bruno Reversade, Kristy Red-Horse
Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function...
September 25, 2017: Developmental Cell
Laina Freyer, Chih-Wei Hsu, Sonja Nowotschin, Andrea Pauli, Junji Ishida, Keiji Kuba, Akiyoshi Fukamizu, Alexander F Schier, Pamela A Hoodless, Mary E Dickinson, Anna-Katerina Hadjantonakis
Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos...
August 29, 2017: Cell Reports
David Coquerel, Frédéric Chagnon, Xavier Sainsily, Lauralyne Dumont, Alexandre Murza, Jérôme Côté, Robert Dumaine, Philippe Sarret, Éric Marsault, Dany Salvail, Mannix Auger-Messier, Olivier Lesur
OBJECTIVES: Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown...
November 2017: Critical Care Medicine
Lena Ho, Marie van Dijk, Sam Tan Jian Chye, Daniel M Messerschmidt, Serene C Chng, Sheena Ong, Ling Ka Yi, Souad Boussata, Grace Hui-Yi Goh, Gijs B Afink, Chin Yan Lim, N Ray Dunn, Davor Solter, Barbara B Knowles, Bruno Reversade
Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis...
August 18, 2017: Science
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