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On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
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Zhibin YAN, Ying SHI, Runling YANG, Jijun XUE, Caiyun FU. ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300033 @article{title="ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways", %0 Journal Article TY - JOUR
ELABELA衍生肽ELA13通过抑制Smad和ERK信号通路减轻肾纤维化1浙江理工大学生命科学与医药学院,浙江省家蚕生物反应器和生物医药重点实验室,中国杭州市,310018 2兰州大学化学化工学院,功能有机分子化学国家重点实验室,中国兰州市,730000 3兰州大学甘肃省新药临床前研究重点实验室,中国医学科学院多肽研究创新单元(2019RU066),中国兰州市,730000 摘要:肾脏纤维化是各种慢性肾脏疾病发展为终末期肾病的关键过程。目前尚无针对肾纤维化的特异性治疗方法。ELA13(氨基酸序列:RRCMPLHSRVPFP)是ELABELA在所有脊椎动物中的保守片段,目前对其生物学活性的研究却很少。本研究评估了ELA13对转化生长因子β1(TGF-β1)处理的NRK-52E细胞和单侧输尿管闭塞(UUO)小鼠的作用效果。首先,体外实验表明在TGF-β1诱导的NRK-52E细胞中,ELA13可以降低纤维化标志物I型胶原(Collagen I)、纤连蛋白(fibronectin)和α-平滑肌肌动蛋白(α-SMA)的表达水平。随后,在UUO诱导的小鼠肾纤维化模型中,我们发现ELA13可以通过降低血清中肌酐和尿素氮的含量来改善肾功能,并通过Masson染色、免疫组织化学、实时定量聚合酶链式反应(RT-PCR)和蛋白质印迹(western blot)的结果证实纤维化标志物和炎症标志物的表达降低了。进一步机制研究发现,ELA13处理可抑制Smad和细胞外调节蛋白激酶(ERK)信号通路。综上所述,ELA13通过抑制Smad和ERK信号通路发挥抗肾纤维化的作用,有望成为抗肾纤维化治疗的候选分子。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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