Biological functions of Elabela, a novel endogenous ligand of APJ receptor

Xu, Jin; Chen, Linxi; Jiang, Zhisheng; Li, Lanfang

doi:10.1002/jcp.26492

Cited by 52 publications

(48 citation statements)

References 88 publications

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“…Previous studies show that ELA is expressed not only in embryos but also in adult kidneys 24 , 29 . In humans, a 54-amino-acid (aa) full length of ELA bears a cleavage to yield a secretory mature form comprised of 32 aa 23 . The amino-acid sequence analysis reveals multiple dibasic sites in the 32-aa ELA (ELA-32), implying more shorten isoforms existing in vivo 38 .…”

Section: Discussionmentioning

confidence: 99%

“…ELABELA/Toddler/Apela (ELA) is a 32-amino-acid peptide as a novel endogenous ligand for the APJ/Apelin receptor 22 . Previous studies demonstrate that ELA plays diverse biological functions in embryonic development [22][23][24][25] . Actually, the expression of ELA is also detected abundantly in adult kidneys 26,27 , especially in renal medulla 28 , suggesting that ELA may have important roles in the kidney.…”

Section: Introductionmentioning

confidence: 99%

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ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

Chen

Liu

et al. 2020

Cell Death Dis

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ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechanism. In DOCA/salt-treated rats, the mRNA level of ELA greatly decreased in the renal medulla. Next, overexpression of ELA in the kidney was found to attenuate DOCA/salt-induced hypertension and renal injury, including lower blood pressure, reversed glomerular morphological damage, decreased blood urea nitrogen (BUN), and blocked the accumulation of fibrotic markers. Mechanistically, ELA overexpression inhibited renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subsequent reactive oxygen species (ROS) production, thus resulted in the blockade of formation and activation of Nod-like receptor protein 3 (NLRP3) inflammasome. The inhibitory effects of ELA on Aldosterone-stimulated NADPH oxidase/ROS/NLRP3 inflammasome pathway were confirmed in the human renal tubular cells. Furthermore, our in vivo and in vitro results showed that the deficiency of the apelin receptor APJ did not influence the antihypertensive effect and blockage to NADPH oxidase/ROS/NLRP3 pathway of ELA. Moreover, in heterozygous ELA knockout mice (ELA+/−), the ELA deficiency remarkably accelerated the onset of DOCA/salt-induced hypertension. Our data demonstrate that ELA prevents DOCA/salt-induced hypertension by inhibiting NADPH oxidase/ROS/NLRP3 pathway in the kidney, which is APJ independent. Pharmacological targeting of ELA may serve as a novel therapeutic strategy for the treatment of hypertensive kidney disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

Chen

Liu

et al. 2020

Cell Death Dis

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“…The putative receptor protein related to angiotensin II receptor type-1 (AT1R), known as APJ, is a G-protein-coupled receptor comprising 380 amino acids in human (O'Dowd et al, 1993). emerged in both embryos and adult organisms, such as dysontogenesis, self-renewing of human embryonic stem cells, endoderm differentiation (Xu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The Apelin/APJ System in Psychosis and Neuropathy

Chen

Wang

2020

Front. Pharmacol.

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Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the Gprotein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy.

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“…A increasing body of evidence supposes that PE as a described mechanism of disease is the Elabela/apelin receptor axis 24,25 . Data from a study by Ho et al illustrated that the ELA–APJ axis contributed to embryonic development and prevented PE in women during pregnancy, which further clarified that the ELA–APJ axis was biologically functional in both embryos and adult organisms 24 .…”

Section: Discussionmentioning

confidence: 99%

ELABELA improves endothelial cell function via the ELA–APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells

Wang¹,

Liang²,

Guo³

et al. 2020

Clin Exp Pharma Physio

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Destruction of endothelial cells (ECs) function is involved in the structural and functional pathophysiological processes of preeclampsia (PE). Vascular endothelial injury may pre‐exist for several years in women that develop PE and may pose increased risks for hypertension, coronary artery disease, and type‐2 diabetes mellitus. Previous findings showed that Elabela (ELA), the endogenous ligand of the apelin (APJ) receptor expressed mainly on ECs, may play a protective role in early pregnancy and prevent PE. However, the exact functional role and molecular mechanisms of ELA are unclear. Here, we aimed to classify whether and how ELA improves EC function via the ELA–APJ axis. Two human umbilical vein endothelial cell (HUVEC) lines, namely HUVECs and EA.hy926, were treated with ELA, and then their cellular activities were studied by performing CCK‐8 tests, scratch‐wound analysis, and tube‐formation assays. Doses of ELA exceeding 0.01 μmol/L markedly improved the cell viability, migration, and tube formation ability of HUVECs and EA.hy926 cells. Western blot analysis indicated that the above effects caused by ELA were related to upregulation of the APJ receptor and activation of PI3K/Akt signalling. Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signalling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA–APJ axis and PI3K/Akt signalling and that ELA shows promise for use in endothelial dysfunction therapy for preventing and treating PE.

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Biological functions of Elabela, a novel endogenous ligand of APJ receptor

Cited by 52 publications

References 88 publications

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

The Apelin/APJ System in Psychosis and Neuropathy

ELABELA improves endothelial cell function via the ELA–APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells

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