ELABELA(ELA),an endogenous ligand of the apelin receptor(also known as apelin peptide jejunum[APJ]),has been shown to decrease in the plasma of patients with diabetic kidney disease(DKD).In the current study,we explor...ELABELA(ELA),an endogenous ligand of the apelin receptor(also known as apelin peptide jejunum[APJ]),has been shown to decrease in the plasma of patients with diabetic kidney disease(DKD).In the current study,we explored the potential function as well as the underlying mechanisms of ELA in DKD.We first found that the ELA levels were decreased in the kidneys of DKD mice.Then,we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin,collagenⅣ,and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells.Furthermore,the autophagy markers,Beclin-1 and LC3-Ⅱ/LC3-Ⅰratio,were significantly impaired in DKD,but the ELA treatment reversed these alterations.Mechanistically,the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine(an autophagy inhibitor).In summary,these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy,potentially serving as a novel therapeutic candidate for DKD.展开更多
BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 ...BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.82000743 and 81700723)the Jiangsu Natural Science Foundation(Grant No.BK20191213).
文摘ELABELA(ELA),an endogenous ligand of the apelin receptor(also known as apelin peptide jejunum[APJ]),has been shown to decrease in the plasma of patients with diabetic kidney disease(DKD).In the current study,we explored the potential function as well as the underlying mechanisms of ELA in DKD.We first found that the ELA levels were decreased in the kidneys of DKD mice.Then,we found that ELA administration mitigated renal damage and downregulated the expression of fibronectin,collagenⅣ,and transforming growth factor-β1 in the db/db mice and the high glucose cultured HK-2 cells.Furthermore,the autophagy markers,Beclin-1 and LC3-Ⅱ/LC3-Ⅰratio,were significantly impaired in DKD,but the ELA treatment reversed these alterations.Mechanistically,the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine(an autophagy inhibitor).In summary,these in vivo and in vitro results demonstrate that ELA effectively protects against DKD by activating high glucose-inhibited renal tubular autophagy,potentially serving as a novel therapeutic candidate for DKD.
基金approved by the Scientific-Ethical Committee of the Mustansiriyah University(Approval No.IRB126).
文摘BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.
