# Renal Aspects of the Apelinergic System: Therapeutic Potential and Mechanisms

**Authors:** Mulan Wang, Jun Yu, Chuanming Xu

PMC · DOI: 10.3390/biom16020184 · Biomolecules · 2026-01-26

## TL;DR

The Apelinergic system protects the kidneys in various diseases and could be a promising target for new therapies.

## Contribution

This review highlights the therapeutic potential of the Apelinergic system in kidney diseases and its mechanisms.

## Key findings

- The Apelinergic system is expressed in kidneys and protects against multiple renal pathologies.
- Increasing Apelin or ELABELA peptides may offer a pharmacological strategy for kidney disease treatment.
- Understanding the system's mechanisms can aid in developing novel renal therapies.

## Abstract

The Apelinergic system (AS) is a crucial endocrine system that plays a vital role in renal physiology and disease. All components of the AS are expressed throughout the kidneys in both humans and rodents. A multitude of studies have consistently shown that the AS exerts a protective effect on the kidneys across a wide spectrum of renal pathologies, encompassing acute kidney injury, chronic kidney disease, diabetic nephropathy, hypertensive kidney injury, cardiorenal syndrome, and renal cell carcinoma. Considering its pivotal role, it shows immense potential as a viable therapeutic target for renal disorders. A deeper mechanistic understanding of the AS will accelerate the rational development of novel therapeutic agents for kidney diseases. In this review, we offer a concise overview of the physiological and pathological roles of the AS in the kidney. Our focus lies on its diuretic effect and its renoprotective action against kidney injury. Enhancing the levels of peripheral Apelin or ELABELA peptides to a certain degree could potentially serve as a promising pharmacological therapeutic strategy for kidney diseases.

## Linked entities

- **Proteins:** APELA (apelin receptor early endogenous ligand)
- **Diseases:** acute kidney injury (MONDO:0002492), chronic kidney disease (MONDO:0005300), diabetic nephropathy (MONDO:0005016), cardiorenal syndrome (MONDO:0044079), renal cell carcinoma (MONDO:0005086)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Avp (arginine vasopressin) [NCBI Gene 11998] {aka Vp, Vsp}, Cpe (carboxypeptidase E) [NCBI Gene 12876] {aka CPH, Cph-1, Cph1, NF-alpha1, fat}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Gpr34 (G protein-coupled receptor 34) [NCBI Gene 23890] {aka Lypsr1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Aqp2 (aquaporin 2) [NCBI Gene 11827] {aka AQP-CD, WCH-CD, cph, jpk}, Furin (furin, paired basic amino acid cleaving enzyme) [NCBI Gene 18550] {aka 9130404I01Rik, Fur, PACE, Pcsk3, SPC1}, Apela (apelin receptor early endogenous ligand) [NCBI Gene 100038489] {aka Ela, Elabela, Ende, Gm10664}, Sirt3 (sirtuin 3) [NCBI Gene 293615], Klf15 (Kruppel-like transcription factor 15) [NCBI Gene 66277] {aka 1810013I09Rik, CKLF, KKLF, hlb444}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, Edn1 (endothelin 1) [NCBI Gene 13614] {aka ET-1, PPET1, preproET}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, Apln (apelin) [NCBI Gene 58812] {aka Apel}, Pcsk2 (proprotein convertase subtilisin/kexin type 2) [NCBI Gene 18549] {aka 6330411F23Rik, Nec-2, Nec2, PC2, Phpp-2, SPC2}, Crh (corticotropin releasing hormone) [NCBI Gene 12918] {aka CRF, Gm1347}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, APELA (apelin receptor early endogenous ligand) [NCBI Gene 100506013] {aka ELA, Ende, tdl}, Agtrap (angiotensin II, type I receptor-associated protein) [NCBI Gene 11610] {aka 3300002E14Rik, AT1R, Atrap, D4Wsu124e}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Nfatc1 (nuclear factor of activated T-cells 1) [NCBI Gene 100361818], Kdr (kinase insert domain protein receptor) [NCBI Gene 16542] {aka 6130401C07, Flk-1, Flk1, Krd-1, Ly73, VEGFR-2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, Nos3 (nitric oxide synthase 3, endothelial cell) [NCBI Gene 18127] {aka 2310065A03Rik, Nos-3, eNOS, ecNOS}, Nedd4l (neural precursor cell expressed, developmentally down-regulated gene 4-like) [NCBI Gene 83814] {aka 1300012C07Rik, NEDD4.2, Nedd4-2, Nedd4b}, Aplnr (apelin receptor) [NCBI Gene 83518] {aka Agtrl1, Apj}, Scnn1a (sodium channel, nonvoltage-gated 1 alpha) [NCBI Gene 20276] {aka ENaC, SCNEA, Scnn1, mENaC}, Tek (TEK receptor tyrosine kinase) [NCBI Gene 21687] {aka Cd202b, Hyk, STK1, Tie-2, Tie2}, Slc9a3 (solute carrier family 9 (sodium/hydrogen exchanger), member 3) [NCBI Gene 105243] {aka 9030624O13Rik, NHE-3, NHE3}, Ighv1-62 (immunoglobulin heavy variable 1-62) [NCBI Gene 668542] {aka IgG, IgM, IgVH, Igh}, Aplnr (apelin receptor) [NCBI Gene 23796] {aka APJ, Agtrl1, msr/apj}, Avpr2 (arginine vasopressin receptor 2) [NCBI Gene 12000] {aka ADHR, DI1, DIR, ND1, V2R, VPV2R}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Apln (apelin) [NCBI Gene 30878] {aka 6030430G11Rik, Apel}, Slc12a1 (solute carrier family 12, member 1) [NCBI Gene 20495] {aka D630042G03Rik, Nkcc2, mBSC1, mNKCC2, urehr3}, LINC02605 (long intergenic non-protein coding RNA 2605) [NCBI Gene 112935892] {aka AS, IL-7, IL-7-AS}, AVPR2 (arginine vasopressin receptor 2) [NCBI Gene 554] {aka ADHR, DI1, DIR, DIR3, NDI, NDI1}, Sirt3 (sirtuin 3) [NCBI Gene 64384] {aka 2310003L23Rik, Sir2l3}, Agt (angiotensinogen) [NCBI Gene 11606] {aka AngI, AngII, Aogen, Serpina8}, Esrra (estrogen related receptor, alpha) [NCBI Gene 293701] {aka ERRalpha, Errra}, APLNR (apelin receptor) [NCBI Gene 187] {aka AGTRL1, APJ, APJR, HG11}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Gnaq (guanine nucleotide binding protein, alpha q polypeptide) [NCBI Gene 14682] {aka 1110005L02Rik, 6230401I02Rik, Dsk1, Dsk10, Galphaq, Gq}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, APLN (apelin) [NCBI Gene 8862] {aka APEL, XNPEP2}
- **Diseases:** renovascular hypertension (MESH:D006978), water retention (MESH:D016055), atherosclerosis (MESH:D050197), coronary heart disease (MESH:D003327), hypertension (MESH:D006973), death (MESH:D003643), APJ deficiencies (MESH:D007153), renal microvascular injury (MESH:D017566), Renal fibrosis (MESH:D005355), albuminuria (MESH:D000419), I/R (MESH:D015427), injury to (MESH:D014947), embryonic lethality (MESH:D020964), CRS (MESH:D059347), inflammation (MESH:D007249), congenital heart disease (MESH:D006330), CKD (MESH:D051436), hyponatremia (MESH:D007010), preeclampsia (MESH:D011225), polydipsia syndrome (MESH:D059606), polyuria (MESH:D011141), renal tubular lesions (MESH:D000141), diabetes (MESH:D003920), hypertrophy (MESH:D006984), atrial fibrillation (MESH:D001281), end-stage renal failure (MESH:D007676), foot process (MESH:D005530), disorders of water metabolism (MESH:D000069578), /R (MESH:C580424), benign tumor (MESH:D009369), renal pathological changes (MESH:D002114), kidney failure (MESH:D051437), CD (MESH:D003424), cardiovascular diseases (MESH:D002318), AKI (MESH:D058186), type 1 diabetes (MESH:D003922), AS (MESH:D015619), heart diseases (MESH:D006331), tumorigenesis (MESH:D063646), OCCC (MESH:D010051), myocardial injury (MESH:D009202), heart failure (MESH:D006333), cardiovascular and renal dysfunctions (MESH:D007674), type 2 diabetes (MESH:D003924), gastric damage (MESH:D013272), sepsis (MESH:D018805), hypoxia (MESH:D000860), renal oncocytoma (MESH:C537750), RCC (MESH:D002292), ADPKD (MESH:D016891), renal tumors (MESH:D007680), proteinuria (MESH:D011507), UUO (MESH:D014517), ischemia (MESH:D007511), tubulointerstitial damage (OMIM:162000), DN (MESH:D003928), cardiovascular malformations (MESH:D018376), myocardial and renal dysfunction (MESH:D006030)
- **Chemicals:** Na+ (MESH:D012964), cyclosporine (MESH:D016572), acid (MESH:D000143), Apelins (MESH:D000073861), K+ (MESH:D011188), Salt (MESH:D012492), AMG986 (-), cisplatin (MESH:D002945), CMF-019 (MESH:C000618332), fatty acid (MESH:D005227), arginine (MESH:D001120), L-NAME (MESH:D019331), aldosterone (MESH:D000450), DOCA (MESH:D064791), PEG (MESH:D011092), prostaglandin E2 (MESH:D015232), streptozocin (MESH:D013311), Pal (MESH:D019308), LPS (MESH:D008070), lipid (MESH:D008055), Water (MESH:D014867), calcium (MESH:D002118), ROS (MESH:D017382), creatinine (MESH:D003404), asymmetric dimethylarginine (MESH:C018524), NO (MESH:D009569), amiloride (MESH:D000584)
- **Species:** Adeno-associated virus (species) [taxon 272636], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Bos taurus (bovine, species) [taxon 9913]
- **Cell lines:** NRK-52E — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0468)

## Full text

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## Figures

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## References

224 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937783/full.md

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Source: https://tomesphere.com/paper/PMC12937783