Apelin/APJ system: A novel potential therapy target for kidney disease

Huang, Zhen; Wu, Lixian; Chen, Linxi

doi:10.1002/jcp.26144

Cited by 50 publications

(48 citation statements)

References 69 publications

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“…It codes a preproapelin of 77 amino acids (Medhurst et al, ), and then this preproapelin is cleaved into polypeptides of varying lengths, including the common Apelin‐36, Apelin‐17, Apelin‐13, Apelin‐12, and so on (Szokodi et al, ; Zhang, Yao, Raizada, O'Rourke, & Sun, ), of which apelin‐12, Apelin‐13, Apelin‐17, Apelin‐36 have endogenous acitivity (Charo et al, ; Esposito et al, ; Horiuchi, Fujii, Kamimura, & Kawashima, ; Pisarenko et al, ). Both apelin and APJ are widely expressed in many tissues, such as heart, kidney, and blood vessels (Li et al, ; Liu, Chen, & Chen, ; Lv et al, ; Xie et al, ; Yu et al, ; Z. Huang, Wu, & Chen, ). A large amount of evidence indicates that the apelin/APJ pathway plays an important role in the regulation of cardiovascular functions (Barnes, Japp, & Newby, ; Galanth, Hus‐Citharel, Li, & Llorens‐Cortes, ; Tycinska, Lisowska, Musial, & Sobkowicz, ; Yu et al, ).…”

Section: Agonists Of Apjmentioning

confidence: 99%

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Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Huang

Chen

et al. 2018

Journal Cellular Physiology

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G-protein-coupled receptors (GPCRs) are recognized as the largest protein receptor superfamily, which are widely distributed in various tissues and organs. In addition, GPCRs are involved in many physiological and pathological longitudinal responses. Studies have indicated that putative receptor protein related to AT1 (APJ receptor) is an orphan GPCRs until its endogenous ligand apelin is found. Recently, Elabela, a new APJ receptor endogenous ligand was also found. Some evidence showed that the APJ receptor is distributed in the central nervous and cardiovascular systems. Moreover, the APJ receptor and its ligand are involved in many physiological functions and pathophysiological effects, making it a promising drug target for future treatment of diseases such as ischemic heart disease, hypertension, heart failure, and others. Although APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we try our best to summarize all agonists and antagonists targeting APJ, including peptides and small molecules. Given the role of apelin/APJ and Elabela/APJ in cardiovascular and other diseases, we believe that the combination of these agonists and antagonists with apelin and Elabela will play a corresponding role in various pathophysiological effects with further development of research.

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Section: Agonists Of Apjmentioning

confidence: 99%

“…In addition, the apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of chronic kidney disease (Z. Huang, Wu et al, 2018).…”

mentioning

confidence: 99%

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Huang

Chen

et al. 2018

Journal Cellular Physiology

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“…Apelin stimulates several metabolic pathways, such as glucose uptake, mitochondrial biogenesis, and fatty acid oxidation, while inhibiting lipolysis and insulin secretion (Boucher et al 2005;Dray et al 2008;O'Carroll et al 2013;Alfarano et al 2015;Bertrand et al 2015). Rapidly, apelin went from an overlooked ORF in a lncRNA to a promising biomarker and therapeutic target in cardiovascular diseases, diabetes, and diabetic complications (Castan-Laurell et al 2011O'Carroll et al 2013;Hu et al 2016;Huang et al 2018). Elevated apelinemia was found in obese patients across several studies, which was suggested to be a compensatory mechanism prior to insulin resistance (Boucher et al 2005;Heinonen et al 2005Heinonen et al , 2009Li et al 2006;Castan-Laurell et al 2008;Dray et al 2008Dray et al , 2010Erdem et al 2008;Soriguer et al 2009;Telejko et al 2010).…”

Section: Smorfs: Mrna or Lncrna Orfs Smaller Than 100 Codonsmentioning

confidence: 99%

Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship

et al. 2018

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Technological advances promise unprecedented opportunities for whole exome sequencing and proteomic analyses of populations. Currently, data from genome and exome sequencing or proteomic studies are searched against reference genome annotations. This provides the foundation for research and clinical screening for genetic causes of pathologies. However, current genome annotations substantially underestimate the proteomic information encoded within a gene. Numerous studies have now demonstrated the expression and function of alternative (mainly small, sometimes overlapping) ORFs within mature gene transcripts. This has important consequences for the correlation of phenotypes and genotypes. Most alternative ORFs are not yet annotated because of a lack of evidence, and this absence from databases precludes their detection by standard proteomic methods, such as mass spectrometry. Here, we demonstrate how current approaches tend to overlook alternative ORFs, hindering the discovery of new genetic drivers and fundamental research. We discuss available tools and techniques to improve identification of proteins from alternative ORFs and finally suggest a novel annotation system to permit a more complete representation of the transcriptomic and proteomic information contained within a gene. Given the crucial challenge of distinguishing functional ORFs from random ones, the suggested pipeline emphasizes both experimental data and conservation signatures. The addition of alternative ORFs in databases will render identification less serendipitous and advance the pace of research and genomic knowledge. This review highlights the urgent medical and research need to incorporate alternative ORFs in current genome annotations and thus permit their inclusion in hypotheses and models, which relate phenotypes and genotypes.

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“…APELIN is the endogenous ligand for the angiotensin I receptor-related protein J receptor (APJ) which is a seven transmembrane G protein-coupled receptor that has 31% amino acid sequence similar to angiotensin II type 1 receptor, but it doesn't bind angiotensin II [1] . Apelin and APJ are expressed in blood vessels, adipose tissue, lungs, heart, and kidneys [2][3][4] . Apelin is produced as a preproapelin formed of 77 amino acids, and then, cleaved by an angiotensin-converting enzyme to form several shorter bioactive peptides as apelin-13, -16, -17, -19 and -36 [5] .…”

Section: Introductionmentioning

confidence: 99%

“…Evidence showed that inflammation and oxidative stress were implicated in the pathogenesis of CRF [14] . But, Pisarenko, Lankin [15] and Huang, Wu [3] found that apelin had anti-inflammatory and antioxidant actions. Thus, we speculated that apelin-13 could prevent or at least delay the development of CRF.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Apelin-13 on Kidney and Platelet Functions in Adenine-Induced Chronic Renal Failure in Rats

Saied¹,

Musa

2018

The Medical Journal of Cairo University

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Background: Apelin and angiotensin I receptor-related protein J receptor (APJ) were found to be expressed in the kidney. Also, in cases of Chronic Renal Failure (CRF), platelet function was found to be affected. Apelin-13 treatment effect on both kidney and platelet functions in cases of CRF was not fully understood. Aim of Study:To investigate the possible protective effect of apelin-13 on kidney and platelet function in adenineinduced CRF in rats.Material and Methods: Rats were divided into three groups of eight rats each as follow: Intact control group received a standard diet for 28 days, adenine treated group received a standard diet added to it adenine (0.75% w/w) for 28 days, and adenine + apelin treated group received a standard diet added to it adenine as in the adenine treated group with a concomitant treatment with apelin-13 for 28 days. Apelin-13 was dissolved in saline immediately before use and was given at a dose of 5µ g/kg body weight/day subcutaneously. 24-hour urine samples were collected, and 24-hour water intake was estimated on the 28 th day of the study, while each rat was kept in a separate metabolic cage. The collected urine samples were measured for volume, total protein, and creatinine levels. After 28 days from the start of the experimental period, rats were fasted overnight, and their blood pressure was measured using the Power Lab. Blood samples were collected and a part of it was placed in heparinized tubes to investigate platelet indices and another part of blood was kept in nonheparinized tubes which were left to clot for 30min at room temperature. Clotted blood was centrifuged at 3000rpm for 15min. The supernatant serum was pipetted off using fine tipped automatic pipettes and stored at -20ºC until assayed.Results: Treatment with adenine (0.75%, w/w) for 28 days caused a significant decrease (p<0.001) in Body Mass Index (BMI) and a significant increase (p<0.001) of the relative kidney weight when compared with that of the control group. On concomitant treatment with apelin-13 and adenine significantly mitigated (p<0.001) the adenine-induced reduction in BMI and the increase in relative kidney weight. Water intake and urine output of adenine treated rats were significantly higher (p<0.001) than that in control rats, while, Conclusion: Apelin-13 treatment improved both kidney and platelet functions, and may give a promising strategy for slowing the progression of CRF and its complications.

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Apelin/APJ system: A novel potential therapy target for kidney disease

Cited by 50 publications

References 69 publications

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship

Protective Effect of Apelin-13 on Kidney and Platelet Functions in Adenine-Induced Chronic Renal Failure in Rats

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