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On-line Access: 2024-04-07

Received: 2023-01-11

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Crosschecked: 2024-04-07

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Caiyun FU

https://orcid.org/0000-0003-4090-885X

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.4 P.341-353

http://doi.org/10.1631/jzus.B2300033


ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways


Author(s):  Zhibin YAN, Ying SHI, Runling YANG, Jijun XUE, Caiyun FU

Affiliation(s):  Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China; more

Corresponding email(s):   fucy03@zstu.edu.cn

Key Words:  ELA13, Kidney fibrosis, Inflammation, Smad, Extracellular signal-regulated kinase (ERK)


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, 2024, 25(4): 341-353.

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author="Zhibin YAN, Ying SHI, Runling YANG, Jijun XUE, Caiyun FU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="4",
pages="341-353",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300033"
}

%0 Journal Article
%T ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways
%A Zhibin YAN
%A Ying SHI
%A Runling YANG
%A Jijun XUE
%A Caiyun FU
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 4
%P 341-353
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300033

TY - JOUR
T1 - ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways
A1 - Zhibin YAN
A1 - Ying SHI
A1 - Runling YANG
A1 - Jijun XUE
A1 - Caiyun FU
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 4
SP - 341
EP - 353
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300033


Abstract: 
kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1 (TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

ELABELA衍生肽ELA13通过抑制Smad和ERK信号通路减轻肾纤维化

闫志斌1,史影2,杨润玲3,薛吉军2,付彩云1,3
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:ELA13;肾纤维化;炎症反应;Smad;细胞外调节蛋白激酶(ERK)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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