Affinage

APELA

Apelin receptor early endogenous ligand · UniProt P0DMC3

Length
54 aa
Mass
6.6 kDa
Annotated
2026-06-09
97 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APELA (Elabela/Toddler/ELA) is a secreted peptide hormone that serves as a high-affinity endogenous ligand for the APJ (APLNR) receptor, where it competes with apelin for the same site, activates inhibitory Gi signaling to suppress forskolin-stimulated cAMP, and drives ERK1/2 phosphorylation (PMID:25995451). Through this APJ axis it regulates cardiovascular physiology — increasing cardiac contractility and inducing coronary vasodilation in an ERK1/2-dependent manner (PMID:26611206) — and genetic ablation in mice produces cardiovascular and vascular remodeling defects together with aberrant erythroid/myeloid marker expression, with epistasis showing APELA acts on early Aplnr-expressing mesoderm independently of apelin (PMID:28854362). The APELA precursor (proELA) is processed by furin into mature isoforms, and disrupting the furin cleavage site alters its biological activity (PMID:32516140, PMID:34455010), with distinct fragments such as ELA-11 signaling through APJ to activate PI3K/AKT and ERK/MAPK and to protect against oxidative and inflammatory stress (PMID:36160397, PMID:32687618). Beyond its receptor-mediated peptide role, the APELA RNA acts independently as a non-coding regulatory transcript in embryonic stem cells, binding hnRNPL to block mitochondrial p53 localization and thereby restrain DNA-damage-induced apoptosis in a manner that does not require its coding capacity (PMID:25936916). APELA also exerts APLNR-independent, p53-linked effects on tumor cell proliferation (PMID:29079036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2015 High

    Established APELA as a bona fide endogenous APJ ligand, answering whether it engages the same receptor as apelin and through which G protein pathway.

    Evidence Radioligand competition with Kd determination, cAMP inhibition and ERK1/2 Western blot, plus in vivo diuresis studies in rats

    PMID:25995451

    Open questions at the time
    • Structural basis of the APELA-APJ interaction not resolved
    • Relative contribution of individual isoforms to receptor activation not dissected
  2. 2015 High

    Revealed a coding-independent function: the APELA RNA itself is a regulatory non-coding RNA controlling the p53 apoptotic response, separating the transcript's role from the peptide's.

    Evidence RNA pulldown with hnRNPL, shRNA depletion, p53 subcellular fractionation, and apoptosis assays in mouse ESCs, with a coding-null mutant

    PMID:25936916

    Open questions at the time
    • Structural detail of the APELA RNA-hnRNPL interaction unknown
    • Whether this RNA function operates outside ESCs unaddressed
  3. 2015 High

    Demonstrated APELA's physiological cardiac role and confirmed ERK1/2 as the effector mediating its inotropic action.

    Evidence Receptor binding in heart tissue and isolated rat heart perfusion with pharmacological ERK1/2 inhibition

    PMID:26611206

    Open questions at the time
    • Cell type within heart mediating contractility not defined beyond non-cardiomyocyte fraction
    • Chronic versus acute effects not distinguished
  4. 2017 High

    Genetic loss-of-function placed APELA in early mesodermal/cardiovascular development and showed it acts independently of apelin on shared APJ-expressing populations.

    Evidence CRISPR/Cas9 null mice, micro-CT, RNA-seq, and Apelin double-mutant epistasis

    PMID:28854362

    Open questions at the time
    • Basis of low penetrance unexplained
    • Molecular driver of erythroid/myeloid dysregulation not identified
  5. 2017 Medium

    Identified an APLNR-independent, p53-linked APELA activity in cancer cells, broadening its mechanism beyond receptor signaling.

    Evidence CRISPR knockout and recombinant peptide addition in OCCC lines lacking APLNR, with cell-cycle and p53 Western blot readouts

    PMID:29079036

    Open questions at the time
    • The receptor or effector mediating the APLNR-independent effect unknown
    • Direct link between APELA and p53 induction not mechanistically defined
  6. 2017 Medium

    Characterized isoform-specific membrane interactions that may shape receptor recognition, providing a biophysical basis for functional differences among isoforms.

    Evidence NMR diffusion/chemical shift and CD spectropolarimetry with micelle systems

    PMID:28132903

    Open questions at the time
    • Functional consequence for receptor binding inferred, not directly shown
    • Relevance to native membranes untested
  7. 2018 Medium

    Mapped an alternative receptor (GPR25) for APELA in non-mammalian vertebrates while showing human GPR25 is not activated, clarifying receptor usage across species.

    Evidence CRE-luciferase cAMP reporter and receptor internalization in HEK293 cells across orthologs

    PMID:29727602

    Open questions at the time
    • Physiological role of GPR25 signaling in vivo unestablished
    • Why human GPR25 is unresponsive not explained
  8. 2020 High

    Defined furin as the maturation protease for proELA and linked processing to mTORC1-dependent anti-tumor activity, connecting precursor handling to function.

    Evidence Site-directed mutagenesis of the furin site, furin inhibition, mTORC1 assays, and kidney tumor xenografts

    PMID:32516140

    Open questions at the time
    • How mature ELA engages mTORC1 mechanistically not resolved
    • Receptor dependence of the anti-tumor effect not pinned down
  9. 2020 Medium

    Showed the ELA-APJ axis promotes endothelial function via PI3K/Akt, extending APELA's vascular signaling repertoire.

    Evidence HUVEC/EA.hy926 viability, migration, tube formation with wortmannin inhibition and Western blot

    PMID:32687618

    Open questions at the time
    • In vivo angiogenic relevance not tested in this study
    • Single-pathway focus leaves crosstalk unaddressed
  10. 2021 Medium

    Determined APELA peptide metabolic stability and the fragment cascade, identifying the bioactive/stable species generated in plasma and kidney.

    Evidence LC-MS/MS metabolic stability assays in human plasma and kidney homogenates

    PMID:34455010

    Open questions at the time
    • Receptor activity of each metabolite not measured here
    • In vivo clearance in humans not validated
  11. 2021 Medium

    Demonstrated APJ-dependent anti-inflammatory signaling via NFκB inhibition in renal endothelium, linking APELA to renoprotection.

    Evidence RGEC treatment with APJ pharmacological blockade, phospho-NFκB Western blot, cytokine and adhesion assays, plus a CRS mouse model

    PMID:34516679

    Open questions at the time
    • Direct receptor-to-NFκB coupling mechanism not defined
    • Single-lab in vivo confirmation
  12. 2022 Medium

    Showed ELA-11 protects cardiomyocytes from oxidative apoptosis through APJ-dependent PI3K/AKT and ERK/MAPK signaling, defining a specific cardioprotective fragment.

    Evidence DOX-injured mouse and cardiomyocyte assays with ML221 APJ antagonist and pathway Western blots

    PMID:36160397

    Open questions at the time
    • Why the 11-residue fragment is preferentially active not explained
    • Long-term cardioprotection not assessed
  13. 2022 Medium

    Established a therapeutic vascular role in pulmonary hypertension via KLF2/eNOS and BMPRII/SMAD4 signaling and EndMT suppression.

    Evidence AAV-ELA32 gene therapy in monocrotaline PAH rats with hemodynamic, histologic, and Western blot readouts

    PMID:35747913

    Open questions at the time
    • Whether effects are APJ-mediated not directly tested
    • Causal ordering of the two signaling axes unresolved
  14. 2024 Medium

    Defined APELA as a regulator of vessel remodeling and arterial specification during regeneration through control of vascular gene programs.

    Evidence Zebrafish fin regeneration with morpholino knockdown and exogenous peptide rescue plus gene expression analysis

    PMID:38355946

    Open questions at the time
    • Direct targets among the regulated genes not distinguished from indirect
    • Receptor mediating regenerative effect not specified
  15. 2025 Medium

    Extended ELA-11's anti-inflammatory action to atherosclerosis via AKT-ER stress inhibition in macrophages, with a delivery strategy improving efficacy.

    Evidence RAW264.7 macrophage assays, AKT-ER stress Western blots, and an mPEG@ELA-11 conjugate in ApoE-/- mice

    PMID:41306397

    Open questions at the time
    • Receptor mediating the macrophage effect not established
    • Mechanistic link between AKT and ER stress not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How APELA's two distinct modes — secreted APJ-ligand peptide signaling and coding-independent RNA regulation of p53 — are coordinated within a single cell, and the identity of the receptor(s) mediating its multiple APLNR-independent activities, remain unresolved.
  • No unified model linking RNA and peptide functions
  • APLNR-independent receptor(s) unidentified
  • No structural model of APELA-receptor or APELA-hnRNPL complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2 GO:0003723 RNA binding 1
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 2
Partners
APLNRFURINGPR25HNRNPL

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 APELA (Elabela/Toddler) binds directly to the APJ receptor with high affinity (Kd = 0.51 nM), competes with apelin for the same binding site, and activates the inhibitory G protein (Gi) pathway by inhibiting forskolin-stimulated cAMP production and inducing ERK1/2 phosphorylation. Chimeric ligand binding assay, radioligand competition, cAMP inhibition assay, ERK1/2 phosphorylation (Western blot), in vivo diuresis/water intake studies in adult rats The Journal of biological chemistry High 25995451
2015 APELA binds to apelin receptors in the adult rodent heart (non-cardiomyocyte fraction), increases cardiac contractility and induces coronary vasodilation, and this inotropic effect is accompanied by ERK1/2 phosphorylation; pharmacological inhibition of ERK1/2 markedly attenuates apela-induced inotropy. Receptor binding in heart tissue, isolated adult rat heart perfusion, Western blot for ERK1/2 phosphorylation, pharmacological ERK1/2 inhibitor experiments Basic research in cardiology High 26611206
2017 Loss of Apela in mice (CRISPR/Cas9 null allele) causes low-penetrance cardiovascular defects, vascular remodeling defects, and aberrant upregulation of erythroid and myeloid markers. Double-mutant analysis showed that Apela signaling impacts early Aplnr-expressing mesodermal populations independently of the alternative ligand Apelin, and combined loss causes lethal cardiac defects. CRISPR/Cas9 knockout, 3D micro-CT, transcriptomics (RNA-seq), double-mutant epistasis analysis Cell reports High 28854362
2015 The Apela RNA functions as a regulatory (non-coding) RNA in mouse embryonic stem cells that interacts with hnRNPL protein, thereby preventing mitochondrial localization and activation of p53. This forms a tri-element negative feedback loop (p53 → represses Apela → Apela/hnRNPL suppresses p53 mitochondrial activation) regulating p53-mediated DNA damage-induced apoptosis. The coding ability of Apela is dispensable for this function. RNA–protein interaction (Apela RNA pulldown with hnRNPL), genetic depletion (shRNA knockdown), co-immunoprecipitation, subcellular fractionation of p53, apoptosis assay in ESCs after DNA damage Cell stem cell High 25936916
2017 APELA promotes tumor cell growth and migration in ovarian clear cell carcinoma (OCCC) through an APLNR-independent pathway in cells lacking APLNR expression, and affects cell-cycle progression in a p53-dependent manner; APELA knockdown induced p53 expression. CRISPR/Cas9 APELA knockout in OCCC cell lines, recombinant APELA peptide addition, cell growth/migration assays, cell-cycle analysis, p53 expression by Western blot Gynecologic oncology Medium 29079036
2020 The APELA precursor (proELA) is cleaved by furin to generate mature ELA; site-directed mutagenesis of the furin cleavage site improves ELA antitumorigenic activity. Mature ELA suppresses kidney tumor cell growth, migration, and survival through mTORC1 signaling activation. Site-directed mutagenesis of furin cleavage site, pharmacological furin inhibition, mTORC1 signaling assays, tumor cell growth/migration assays in vitro, xenograft mouse model with sunitinib combination JCI insight High 32516140
2017 Apela isoforms (apela-54, -32, and -11) exhibit distinct membrane-binding behaviors: apela-32 interacts with DPC, SDS, and LPPG micelles (inducing α-helical character), while apela-11 interacts preferentially with SDS and LPPG micelles (inducing β-turn character), indicating isoform- and headgroup-dependent membrane interactions that may influence apelin receptor recognition. NMR spectroscopy (pulsed-field gradient diffusion NMR, chemical shift perturbation), circular dichroism (CD) spectropolarimetry Biochimica et biophysica acta. Biomembranes Medium 28132903
2021 Apela inhibits angiotensin II-induced inflammatory responses in renal glomerular endothelial cells (including MCP-1, TNF-α, ICAM-1, VCAM-1 expression and THP-1 cell adhesion) by inhibiting the NFκB signaling pathway; blockade of the APJ receptor abolishes these inhibitory effects, confirming APJ-dependence. In vitro cell treatment (RGECs), Western blot for phospho-NFκB, cytokine measurement, APJ inhibitor (pharmacological blockade), THP-1 adhesion assay; in vivo CRS mouse model FASEB journal Medium 34516679
2022 ELA-11 (the furin-cleaved 11-residue fragment of APELA) protects cardiomyocytes against oxidative stress-induced apoptosis through PI3K/AKT and ERK/MAPK signaling pathways, and its protective effect is mediated through the APJ receptor (blocked by ML221, an APJ antagonist). In vivo DOX-injured mouse model, in vitro cardiomyocyte assays with DOX and CoCl2, Western blot for PI3K/AKT and ERK/MAPK, pharmacological APJ antagonist (ML221) blocking experiment Frontiers in pharmacology Medium 36160397
2020 ELABELA improves endothelial cell function (viability, migration, tube formation) via the ELA–APJ axis by activating PI3K/Akt signaling; the PI3K inhibitor wortmannin blocks ELA-induced effects and also blocks ELA-induced APJ receptor upregulation. HUVEC and EA.hy926 cell treatment, CCK-8 viability, scratch-wound, tube formation assays, Western blot for PI3K/Akt, pharmacological PI3K inhibition (wortmannin) Clinical and experimental pharmacology & physiology Medium 32687618
2018 In non-mammalian vertebrates (zebrafish, spotted gar, pigeon), APELA peptides activate GPR25 (an orphan GPCR) to inhibit cAMP production and induce receptor internalization; human GPR25 was NOT activated by Apela under the same conditions. pGL3-CRE-luciferase reporter assay for cAMP inhibition, confocal microscopy for receptor internalization, heterologous expression in HEK293 cells Biochemical and biophysical research communications Medium 29727602
2021 ELA-32 (Apela) in human plasma has a half-life of ~47 min and in kidney homogenates ~44 s. The primary metabolic fragments generated include ELA-11, ELA-16, ELA-19, and ELA-20; ELA-16 was identified as a potentially more stable fragment. LC-MS/MS (Orbitrap) metabolic stability assay in human plasma and kidney homogenates, PEAKS Studio peptide fragment analysis Peptides Medium 34455010
2022 Apela gene therapy (AAV-ELA32) in monocrotaline-induced pulmonary arterial hypertension rats upregulates KLF2/eNOS and BMPRII/SMAD4 signaling in pulmonary arterioles, inhibits endothelial-to-mesenchymal transition, and reduces pulmonary arteriolar muscularization. AAV-mediated gene delivery, right ventricular systolic pressure measurement, histopathology, immunofluorescence, Western blotting for KLF2/eNOS and BMPRII/SMAD4 FASEB journal Medium 35747913
2019 Two rare variants in the 5'-UTR of the APELA gene (c.-306A>G and c.-145A>G) impair transcriptional activity of APELA by altering promoter function, as demonstrated by luciferase reporter assays in HEK293 and HTR-8/SVneo cells. Sanger sequencing, luciferase reporter assay in HEK293 and HTR-8/SVneo cells Prenatal diagnosis Low 30719741
2024 In zebrafish fin regeneration, Apela selectively accumulates in newly formed fin tissue and vessels; morpholino-mediated knockdown of Apela prevents vessel remodeling, while exogenous Apela peptide mediates plexus repression and promotes arterial development in regenerated fins. Apela also regulates expression of vascular remodeling genes including VWF, IGFBP3, ESM1, VEGFR2, Apln, and Aplnr. In vivo fin regeneration model in zebrafish, morpholino knockdown, exogenous peptide rescue, gene expression analysis Scientific reports Medium 38355946
2025 ELA-11 suppresses macrophage foam cell formation, M1 polarization, and apoptosis via inhibition of the AKT–endoplasmic reticulum (ER) stress pathway; mPEG@ELA-11 (a pH-responsive conjugate) reduces atherosclerotic plaque area more effectively than free ELA-11 in ApoE-/- mice. In vitro RAW264.7 macrophage assays (foam cell formation, polarization, apoptosis), Western blot for AKT-ER stress pathway, in vivo ApoE-/- mouse atherosclerosis model, pH-responsive release characterization BME frontiers Medium 41306397

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. Cancer research 273 2460224
1980 Detection of IgM antibodies to cytomegalovirus (CMV) using an enzyme-labelled antigen (ELA). The Journal of general virology 107 6255087
2015 Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic research in cardiology 100 26611206
2015 Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling. The Journal of biological chemistry 98 25995451
2013 Role of ELA region in auto-activation of mutant KIT receptor: a molecular dynamics simulation insight. Journal of biomolecular structure & dynamics 94 23782055
2015 An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells. Cell stem cell 81 25936916
2017 Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives. Cell reports 60 28854362
2010 Mutations in SCARF2 are responsible for Van Den Ende-Gupta syndrome. American journal of human genetics 52 20887961
1987 The adenovirus Ela gene induces differentiation of F9 teratocarcinoma cells. Molecular and cellular biology 47 2439896
1990 The embryonal carcinoma stem cell Ela-like activity involves a differentiation-regulated transcription factor. Nucleic acids research 46 2140887
1998 Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection. Journal of virology 42 9811694
1988 Association between equine leucocyte antigens (ELA) and equine sarcoid tumors in the population of Swedish halfbreds and some of their families. Veterinary immunology and immunopathology 41 3252614
2018 ELABELA/APELA Levels Are Not Decreased in the Maternal Circulation or Placenta among Women with Preeclampsia. The American journal of pathology 40 29803833
2011 Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 22178996
2020 Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility. Stem cell research & therapy 34 32028995
2020 ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation. JCI insight 34 32516140
2017 APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner. Gynecologic oncology 33 29079036
2016 Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. PLoS genetics 32 27187611
2011 Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome. Molecular syndromology 31 22140376
1983 Population studies on the ELA system in American standardbred and thoroughbred mares. Animal blood groups and biochemical genetics 31 6660596
1988 Chromosomal localization of the major histocompatibility complex of the horse (ELA) by in situ hybridization. Immunogenetics 28 3169882
2020 Apela improves cardiac and renal function in mice with acute myocardial infarction. Journal of cellular and molecular medicine 27 32686917
2017 Apela exhibits isoform- and headgroup-dependent modulation of micelle binding, peptide conformation and dynamics. Biochimica et biophysica acta. Biomembranes 27 28132903
2022 ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways. Frontiers in pharmacology 25 36160397
2021 Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer. Frontiers in oncology 23 33912466
1989 Mediation of the induction of immunologic unresponsiveness following antigen pretreatment by a CD4 (W3/25+) T cell appearing transiently in the splenic compartment and subsequently in the TDL. Transplantation 23 2523107
1989 Cooperative binding of two E2F molecules to an Ela-responsive promoter is triggered by the adenovirus Ela, but not by a cellular Ela-like activity. The EMBO journal 22 2531078
2019 APELA Expression in Glioma, and Its Association with Patient Survival and Tumor Grade. Pharmaceuticals (Basel, Switzerland) 21 30917521
2013 Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts. Oncotarget 21 23328228
2011 Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome. American journal of medical genetics. Part A 21 21990121
2008 Transfection efficiency of TDL compound in HUVEC enhanced by ultrasound-targeted microbubble destruction. Ultrasound in medicine & biology 19 18524464
1994 Pancreatic carcinomas of acinar and mixed acinar/ductal phenotypes in Ela-1-myc transgenic mice do not contain c-K-ras mutations. The American journal of pathology 19 8080049
2020 ELABELA improves endothelial cell function via the ELA-APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells. Clinical and experimental pharmacology & physiology 17 32687618
2002 Testis-specific expression of a novel mouse defensin-like gene, Tdl. Mechanisms of development 17 12128228
2023 A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide. Ageing research reviews 16 37776977
2022 ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis. Molecular biology reports 16 36129600
2014 Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer. The Journal of pathology 16 24889936
2003 Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge. Vaccine 15 12531649
1994 CBF mediates adenovirus Ela trans-activation by interaction at the C-terminal promoter targeting domain of conserved region 3. Oncogene 15 7970730
2005 Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts. Carcinogenesis 14 16280331
2020 APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells. Anticancer research 13 32014904
2018 The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates. Biochemical and biophysical research communications 13 29727602
2014 Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion. American journal of medical genetics. Part A 13 24478002
1987 Evidence of a second polymorphic ELA class I (ELA-B) locus and gene order for three loci of the equine major histocompatibility complex. Animal genetics 13 2959176
1994 Cell lines derived from pancreatic tumors of Tg(Ela-1-SV40E)Bri18 transgenic mice express somatostatin and T antigen. Carcinogenesis 12 7904904
2021 Apela inhibits systemic and renal inflammatory reactions in mice with type I cardiorenal syndrome. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 34516679
2020 Emerging roles of APLN and APELA in the physiology and pathology of the female reproductive system. PeerJ 11 33240613
2019 Optimization of Extraction Technology of Majun Mupakhi Ela and its Effect on Hydrocortisone-induced Kidney Yang Deficiency in Mice. Scientific reports 11 30874604
1985 Simple detection of antibodies to different viruses using rheumatoid factor and enzyme-labelled antigen (ELA). Journal of virological methods 11 3884644
2021 Further delineation of van den Ende-Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome. American journal of medical genetics. Part A 10 33783941
2019 Apela Promotes Cardiomyocyte Differentiation from Transgenic Human Embryonic Stem Cell Lines. Applied biochemistry and biotechnology 10 31025171
2016 Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders. American journal of medical genetics. Part A 10 27375131
2014 Small proteins, big roles: the signaling protein Apela extends the complexity of developmental pathways in the early zebrafish embryo. BioEssays : news and reviews in molecular, cellular and developmental biology 10 24924601
2002 A second locus and new alleles in the major histocompatibility complex class II (ELA-DQB) region in the horse. Animal genetics 10 12030922
2001 Genetic variation of the second exon of ELA-DRB genes in Argentine Creole horses. Animal genetics 10 11683711
1993 DNA sequence analysis of serologically detected ELA class II haplotypes at the equine DQ beta locus. Animal genetics 10 8363103
2022 Apela gene therapy alleviates pulmonary hypertension in rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 35747913
2021 In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA. Peptides 9 34455010
2011 Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia. Pediatric blood & cancer 9 21618407
1987 Molecular genetic analysis of the major histocompatibility complex in an ELA typed horse family. Animal genetics 9 2894785
2022 A highly selective colorimetric and fluorescent probe Eu(tdl)2abp for H2S sensing: Application in live cell imaging and natural water. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 8 35917617
2019 Apela/Elabela/Toddler: New perspectives in molecular mechanism of heart failure. Global cardiology science & practice 8 31799290
2018 Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae as a feature of Van Den Ende-Gupta syndrome: a case report. BMC medical genetics 8 29378527
2023 Reduced Apela/APJ system expression in patients with pulmonary artery hypertension secondary to chronic obstructive pulmonary disease. Heart & lung : the journal of critical care 7 36669444
2020 Expression characteristics and regulatory mechanism of Apela gene in liver of chicken (Gallus gallus). PloS one 7 32915867
2003 Analysis of ELA-DQB exon 2 polymorphism in Argentine Creole horses by PCR-RFLP and PCR-SSCP. Journal of veterinary medicine. A, Physiology, pathology, clinical medicine 7 12887619
2001 Stability and CTL-activity of P40/ELA melanoma vaccine candidate. Biologicals : journal of the International Association of Biological Standardization 7 11851331
2015 The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires. Immunogenetics 6 26399241
2013 [Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 6 24010364
1993 Evaluation of c-K-ras in pancreatic carcinomas from Ela-1, SV40E transgenic mice. Carcinogenesis 6 8269641
2024 Apela promotes blood vessel regeneration and remodeling in zebrafish. Scientific reports 5 38355946
2019 Variants in the 5'-UTR of APELA gene in women with preeclampsia. Prenatal diagnosis 5 30719741
2008 Development of an ELA-DRA gene typing method based on pyrosequencing technology. Tissue antigens 5 18764814
2010 A conserved segmental duplication within ELA. Animal genetics 4 21070294
2025 mPEG@ELA-11 Alleviates Atherosclerosis via AKT-ER Stress-Mediated Macrophage Modulation. BME frontiers 3 41306397
2022 Two novel variants in SCARF2 gene underlie van den Ende-Gupta syndrome. American journal of medical genetics. Part A 3 35224863
2018 Characterization, tissue distribution of apela and periprandial, fasting and refeeding changes of apela mRNA in Siberian sturgeon Acipenser baerii. Journal of fish biology 3 29956323
1988 Serological and genetic study of the ELA W21 specificity. Animal genetics 3 2466423
2025 Comprehensive characterization of the chemical composition of Ela tablet and its metabolites, with molecular docking screening of potential bioactive components for erectile dysfunction treatment. Journal of pharmaceutical and biomedical analysis 2 40056491
2024 Clinical Significance of Apela in Acute Cardiorenal Insuffiency of Chronic Heart Failure. Kidney & blood pressure research 2 38237563
2024 Analysis of clinical characteristics of different types of lung function impaiement in TDL patients. BMC pulmonary medicine 2 38914991
2023 The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats. Peptides 2 37245722
2009 Introduction of a three-dimensional and layered (TDL) culture, a novel primary co-culture method for ameloblasts and pulp-derived cells. Archives of histology and cytology 2 20513981
1994 A comparison study of the EF-18 agar/Hydrophobic Grid Membrane Filter (HGMF) method and the enzyme linked antibody (ELA)/HGMF method to the HPB standard method in the isolation of Salmonella. International journal of food microbiology 2 7811575
2025 Evaluation of the effect of Ela tablets in the treatment of diabetic nephropathy based on rat experiments and screening strategy for quality markers of Ela tablets targeting aldose reductase. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1 39793182
2025 Remote Ischemic Conditioning Attenuates Apoptosis, the Inflammatory Response, and Reperfusion Injury in Ischemic-Stroke Model Rats via the ELA-Apelin-APJ System. Journal of integrative neuroscience 1 40919633
2022 A Case-Control Study of the APELA Gene and Hypertensive Disorders of Pregnancy. Medicina (Kaunas, Lithuania) 1 35630008
2012 ELA-DRA polymorphisms are not associated with Equine Arteritis Virus infection in horses from Argentina. Research in veterinary science 1 22534582
2004 Isotope selective analysis of CO(2) with tunable diode laser (TDL) spectroscopy in the NIR. The Analyst 1 15284924
1988 Analysis of a horse family with a crossing-over between the ELA complex and the A blood group system. Animal genetics 1 2967646
2026 Serum pharmacochemistry and network pharmacology reveal multi-pathway mechanisms of Ela Tablet against renal fibrosis in diabetic nephropathy. Fitoterapia 0 41780760
2026 Cardioprotective Effect of Apelin and Apela: The Receptor and Signaling Mechanism. Current reviews in clinical and experimental pharmacology 0 42003195
2026 Substrate-Binding Site Engineering of Thermomyces dupontii Lipase (TDL) to Improve Selectivity for the Synthesis of Functional sn-1,3-Diacylglycerol. Journal of agricultural and food chemistry 0 42011928
2026 Mycobacterium vaccae NCTC 11659 attenuates early life adversity (ELA)-induced hippocampal neuroinflammation in mice. Neuroimmunomodulation 0 42166396
2026 Discriminative Ability and Clinical Associations of Serum SIRT1, SIRT3, Apelin, and ELA in Patients with Diabetic Foot Infection. Life (Basel, Switzerland) 0 42195360
2026 Syndrome of the Month: Van den Ende-Gupta Syndrome: Gestalt Diagnosis, Outcomes, and Recommendations. American journal of medical genetics. Part A 0 42231755
2025 Inhibition of the Microglial Phagocytic Receptor MerTK Underlies ELA-induced Changes in Synapses and Behavior in Male Mice. bioRxiv : the preprint server for biology 0 40791556

Missed literature

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