# ELABELA: A Potential Therapeutic Target for Ischemia–Reperfusion Injury **Authors:** Wan Li, Cuicui Meng, Shujun Yang, Yibei Xie, Zijie Huang, Tong Wang PMC · DOI: 10.3390/biom16020301 · Biomolecules · 2026-02-14 ## TL;DR ELABELA, a hormone, shows promise in protecting tissues from damage caused by restored blood flow after ischemia. ## Contribution This review highlights ELABELA's novel role in reducing ischemia–reperfusion injury across multiple organs. ## Key findings - ELABELA is a cytoprotective ligand of the APJ receptor. - Research shows ELABELA mitigates IRI in various organ systems. - ELABELA is expressed in both adult and embryonic tissues. ## Abstract Ischemia–reperfusion injury (IRI) refers to a paradoxical pathological process in which ischemic tissues or organs sustain further damage upon the restoration of blood flow and is clinically commonly observed in the peripheral vascular systems and various vital organs. In 2013, the endogenous peptidic hormone ELABELA (ELA) was identified as a novel native ligand of the APJ G protein-coupled receptor, alongside apelin. ELA is constitutively expressed in a range of adult and embryonic tissues and plays a role in numerous physiological and pathological processes. In recent years, a rapidly growing body of research has highlighted the cytoprotective properties of ELA against IRI. In this review, we synthesize current research on the protective role of ELA in mitigating IRI across multiple organ systems. ## Linked entities - **Proteins:** APELA (apelin receptor early endogenous ligand), APLNR (apelin receptor) - **Diseases:** ischemia–reperfusion injury (MONDO:0005203) ## Full-text entities - **Genes:** Bax (BCL2-associated X protein) [NCBI Gene 12028], Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, FTH1 (ferritin heavy chain 1) [NCBI Gene 2495] {aka FHC, FTH, FTHL6, HFE5, NBIA9, PIG15}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, Apela (apelin receptor early endogenous ligand) [NCBI Gene 100038489] {aka Ela, Elabela, Ende, Gm10664}, APELA (apelin receptor early endogenous ligand) [NCBI Gene 100506013] {aka ELA, Ende, tdl}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Tie1 (tyrosine kinase with immunoglobulin-like and EGF-like domains 1) [NCBI Gene 21846] {aka D430008P04Rik, TIE, tie-1}, CTSS (cathepsin S) [NCBI Gene 1520], TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, JAG1 (jagged canonical Notch ligand 1) [NCBI Gene 182] {aka AGS, AGS1, AHD, AWS, CD339, CMT2HH}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, ARRB1 (arrestin beta 1) [NCBI Gene 408] {aka ARB1, ARR1}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CTDSP1 (CTD small phosphatase 1) [NCBI Gene 58190] {aka NIF3, NLI-IF, NLIIF, SCP1}, SLC8A1 (solute carrier family 8 member A1) [NCBI Gene 6546] {aka NCX1}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, APLNR (apelin receptor) [NCBI Gene 187] {aka AGTRL1, APJ, APJR, HG11}, MIR124-3 (microRNA 124-3) [NCBI Gene 406909] {aka MIRN124-3, MIRN124A3, mir-124-3}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Angpt1 (angiopoietin 1) [NCBI Gene 11600] {aka 1110046O21Rik, Ang-1, Ang1}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, APLN (apelin) [NCBI Gene 8862] {aka APEL, XNPEP2}, NOTCH3 (notch receptor 3) [NCBI Gene 4854] {aka CADASIL, CADASIL1, CARASIL1, CASIL, FPLD1, IMF2}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, NF1 (neurofibromin 1) [NCBI Gene 4763] {aka NFNS, VRNF, WSS}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, MPO (myeloperoxidase) [NCBI Gene 4353], CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, TRAF1 (TNF receptor associated factor 1) [NCBI Gene 7185] {aka EBI6, MGC:10353}, KLF15 (KLF transcription factor 15) [NCBI Gene 28999] {aka KKLF}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, VN1R17P (vomeronasal 1 receptor 17 pseudogene) [NCBI Gene 441931] {aka GPCR}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Aplnr (apelin receptor) [NCBI Gene 23796] {aka APJ, Agtrl1, msr/apj}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1} - **Diseases:** Fibrosis (MESH:D005355), cerebral lesion (MESH:D002539), injury to (MESH:D014947), Inflammation (MESH:D007249), edema (MESH:D004487), CKD (MESH:D051436), neuroinflammation (MESH:D000090862), preeclampsia (MESH:D011225), liver fibrosis (MESH:D008103), cerebral ischemia (MESH:D002545), tumor (MESH:D009369), renal insufficiency (MESH:D051437), acute stroke (MESH:D020521), AKI (MESH:D058186), multiple organ dysfunction syndrome (MESH:D009102), STEMI (MESH:D000072657), sclerosis (MESH:D012598), fever (MESH:D005334), Ischemia (MESH:D007511), hypertensive (MESH:D006973), occlusion (MESH:D001157), ELA deficiency (MESH:D007153), death (MESH:D003643), Ischemia-Reperfusion Injury (MESH:D015427), placental insufficiency (MESH:D010927), acidosis (MESH:D000138), myocardial ischemia (MESH:D017202), end organ disease (MESH:C564816), myocardial infarction (MESH:D009203), HI (MESH:C538424), cardiac agenesis (MESH:D006331), ischemic reperfusion injury (MESH:D015428), infarct (MESH:D007238), chronic diseases (MESH:D002908), sepsis (MESH:D018805), tissue injury (MESH:D017695), necrosis (MESH:D009336), diabetic nephropathy (MESH:D003928), cardiovascular anomalies (MESH:D018376) - **Chemicals:** oxygen (MESH:D010100), lipid peroxide (MESH:D008054), HI (MESH:D006639), lactate (MESH:D019344), iron (MESH:D007501), water (MESH:D014867), 8-OHdG (MESH:D000080242), 4-HNE (MESH:C027576), Na+ (MESH:D012964), doxorubicin (MESH:D004317), protons (MESH:D011522), Ca2+ (-), MDA (MESH:D008315), DOCA (MESH:D064791), lipid (MESH:D008055), GSH (MESH:D005978), ATP (MESH:D000255), ROS (MESH:D017382), calcium (MESH:D002118), glucose (MESH:D005947) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12937643/full.md ## Figures 5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937643/full.md ## References 93 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937643/full.md --- Source: https://tomesphere.com/paper/PMC12937643