Elabela alleviates diabetic kidney disease by regulating aquaporin 2 / 中华内分泌代谢杂志

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.

Associação entre os Níveis Séricos de Elabela e Oclusão Total Crônica em Pacientes com Angina Pectoris Estável / Association Between Serum Elabela Levels and Chronic Totally Occlusion in Patients with Stable Angina Pectoris

Resumo Fundamento: Os efeitos benéficos do elabela no sistema cardiovascular foram demonstrados em estudos. Objetivo: Comparar os níveis séricos de elabela de pacientes com oclusão total crônica (OTC) com pacientes controle com artérias coronárias normais e investigar se há correlação com o desenvolvimento colateral. Métodos: Estudo transversal e prospectivo. O estudo incluiu cinquenta pacientes (28,0% mulheres, idade média 61,6±7,3 anos) com OTC em pelo menos um vaso coronário e 50 pacientes (38% mulheres, idade média 60,7±6,38 anos) com artérias coronárias normais. Os pacientes do grupo OTC foram divididos em dois grupos: Rentrop 0-1, composto por pacientes com fraco desenvolvimento colateral e Rentrop 2-3, composto por pacientes com bom desenvolvimento colateral. Além da idade, sexo, características demográficas e exames laboratoriais de rotina dos pacientes, foram medidos os níveis de elabela. Resultados: As características demográficas e os valores laboratoriais mostraram-se semelhantes em ambos os grupos. Ao passo que o nível médio de NT-proBNP e troponina estava maior no grupo OTC, o nível médio de elabela estava menor (p<0,05 para todos). Na análise de regressão multivariada, os níveis de NT-proBNP e elabela foram considerados preditores independentes para OTC. Além disso, o nível de elabela apresentou-se estatisticamente maior em pacientes do grupo Rentrop 2-3 em comparação com os pacientes do grupo Rentrop 0-1 (p<0,05). Conclusões: Em nosso estudo, mostramos que o nível médio de elabela estava baixo em pacientes com OTC em comparação com pacientes normais. Além disso, constatamos que o nível de elabela é inferior em pacientes com desenvolvimento colateral fraco em comparação com pacientes com bom desenvolvimento colateral. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background: The beneficial effects of Elabela on the cardiovascular system have been shown in studies. Objective: To compare serum Elabela levels of chronic total occlusion (CTO) patients with control patients with normal coronary arteries, and to investigate whether there is a correlation with collateral development. Methods: The study was planned cross-sectionally and prospectively. Fifty patients (28.0% female, mean age 61.6±7.3years) with CTO in at least one coronary vessel and 50 patients (38% female, mean age 60,7±6.38 years) with normal coronary arteries were included in the study. Patients in the CTO group were divided into two groups as Rentrop 0-1, those with weak collateral development, and Rentrop 2-3 with good collateral development. In addition to the age, sex, demographic characteristics and routine laboratory tests of the patients, Elabela levels were measured. Results: Demographic characteristics and laboratory values were similar in both groups. While the mean NT-proBNP and troponin were higher in the CTO group, the Elabela mean was lower (p <0.05 for all). In the multivariate regression analysis, NT-proBNP and Elabela levels were found to be independent predictors for CTO. Also, Elabela level was found to be statistically higher in Rentrop class 2-3 patients compared to Rentrop class 0-1 patients (p<0.05). Conclusion: In our study, we showed that the average Elabela level was low in CTO patients compared to normal patients. In addition, we found the level of Elabela to be lower in patients with weak collateral development compared to patients with good collateral development. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Research Progress on Role and Mechanism of Elabela in Organ Fibrosis / 中国医学科学院学报

Elabela is a newly discovered peptide in recent years.It is the endogenous ligand of Apelin receptor(APJ)and plays an important role in embryonic development and adult organs.Elabela-APJ axis is closely related to organ fibrosis.Elabela can protect the functions of heart and kidney by antagonizing renin-angiotensin system and regulating blood pressure.In addition,it can prevent kidney and heart fibrosis by down-regulating the expression of fibrosis and inflammatory factors.However,there is a positive correlation between the level of Elabela and the degree of liver fibrosis,suggesting that Elabela may play a role in promoting liver fibrosis.This review aims to explore the role of Elabela-APJ axis in renal fibrosis,cardiac fibrosis,and liver fibrosis,and to provide a new therapeutic target for organ fibrosis.

Elabela promotes differentiation of wharton’s jelly-derived mesenchymal stem cells into cardiomyocyte-like cells / 中国组织工程研究

BACKGROUND: Elabela is a new type of endogenous receptor of APJ discovered in recent years. It is widely distributed in the adult cardiovascular system and has a certain influence on cardiovascular diseases. However, the effect of Elabela on the differentiation of stem cells into cardiomyocytes and the expression of APJ in cardiomyocyte differentiation has not been studied yet. OBJECTIVE: To investigate the effect of Elabela on the differentiation of Wharton’s jelly-derived mesenchymal stem cells into cardiomyocytes. METHODS: The frozen mesenchymal stem cells were resuscitated. 5-Azacytidine was used to induce Wharton’s jelly-derived mesenchymal stem cells to differentiate into cardiomyocytes when the cell confluence reached 80%-90%. After 24 hours, the medium was replaced by low-glucose medium containing Elabela and 10% fetal bovine serum in the experimental group, and by low-glucose medium containing 10% fetal bovine serum in the control group. At 7, 14, 21, and 28 days after induction, cell morphology was observed. The total RNA and total protein of each group were collected. The myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein expression levels were detected by real-time fluorescent quantitative PCR and western blot assay. The expression of APJ in the induced cardiomyocytes was detected by real-time fluorescent quantitative PCR and flow cytometry. RESULTS AND CONCLUSION: (1) The expression levels of myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein were higher in the experimental group than in the control group in all stages of differentiation, and the expression of APJ was also higher in the experimental group than in the control group. (2) In summary, Elabela plays a certain promoting role in the differentiation of Wharton’s jelly-derived mesenchymal stem cells into oriented cardiomyocytes. Elabela, as another agonist of APJ, can promote the expression of APJ during the induced cell differentiation.

Progress in research of the structure and function of Elabela/APJ signal / 药学学报

Elabelas/Toddlers belong to a group of endogenous active peptides recently discovered from zebrafish. The sequences of these peptides have 25% homology to Apelin. These peptides regulate physiological functions of organisms through putative protein receptors related to the angiotensin receptor AT1 (APJ). Functional roles of Elabela include early embryonic development, angiogenesis, fluid homeostasis, and feeding or dietary behavior control. Elabela also participates in the development of many diseases, such as heart failure, preeclampsia, acute kidney injury, hypertension, and diabetes. Increasingly, studies have shown that Elabela/APJ signaling can promote normal development of early embryos, including differentiation of mesoderm and endoderm, and formation of cardiac morphology and function. At the same time, the signaling can also promote angiogenesis or migration and proliferation of tumor cells. Here we describe the molecular structure, biological characteristics, functions and application prospects of Elabela/APJ signaling.