Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-alpha From Proteasomal Degradation

doi:10.3389/fphys.2020.517912

科研成果详情

题名	Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-alpha From Proteasomal Degradation
作者	Shentu, Yangping 1; Jiang, Huanchang 2; Liu, Xiaoyuan2; Chen, Hao2; Yang, Dicheng 2; Zhang, Jinqi 3; Cheng, Chen 2; Zheng, Yulin2; Zhang, Yang 2; Chen, Chaosheng4; Zheng, Chenfei4; Zhou, Ying 4
发表日期	2020-12-16
发表期刊	FRONTIERS IN PHYSIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	peritoneal dialysis peritoneal fibrosis angiogenesis HIF1-α pathway nestin
其他关键词	MESENCHYMAL TRANSITION ; EXPRESSION ; CELLS ; STEM ; HIF-1-ALPHA ; STATE ; TWIST ; VEGF ; EMT
摘要	Background Peritoneal dialysis (PD) is a treatment for end stage renal disease patients, but it can also cause peritoneal fibrosis. Nestin is known as a neural stem cell marker and it has many functions. The hypoxia induced factor (HIF) signaling pathway can be activated under hypoxia conditions, leading to the overexpression of some angiogenesis related genes. The aim of our study is to demonstrate Nestin's role in the development of peritoneal fibrosis (PF), and to provide a new target (Nestin) to treat PF. Methods PD mice models were constructed by an intraperitoneal administration of PDS at 10 ml/100g/d for 4 weeks. Nestin-positive cells were isolated from peritonea of Nestin-GFP mice by flow cytometry. The relationship of Nestin and HIF1-alpha-VEGFA pathway was detected by Nestin knockdown, Co-immunoprecipitation and immunofluorescence. Also, proteasomal activity was demonstrated by CHX and MG132 application, followed by Western blotting and Co-immunoprecipitation. Results In our experiments, we found that Nestin expression resulted in PF. Also, HIF1-alpha/VEGFA pathway was activated in PF. Nestin knockdown reduced the level of HIF1-alpha. Nestin directly bound to HIF1-alpha and protected HIF1-alpha from proteasomal degradation. Overexpression of HIF1-alpha reverts the fibrosis levels in Nestin-knockdown cells. In brief, Nestin inhibited the degradation of HIF1-alpha by mitigating its ubiquitination level, leading to the activation of HIF1-alpha signaling pathway, and eventually promoted PF. Conclusion We found a novel mechanism of PF that Nestin promotes by protecting HIF1-alpha from proteasomal degradation. Taken together, our key findings highlight a novel mechanism by which the silencing of Nestin hinders HIF1- alpha -induced PF.
资助项目	Wenzhou Municipal Science and Technology Bureau of China [ZS2017008, Y20180159, Y2020024]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LQ19H050002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31900685]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1664-042X
卷号	11 页码:517912
DOI	10.3389/fphys.2020.517912
页数	11
WOS类目	Physiology
WOS研究方向	Physiology
WOS记录号	WOS:000603390400001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33391003
PMC记录号	PMC7772359
SCOPUSEID	2-s2.0-85098510034
通讯作者地址	[Zheng, Chenfei]Department of Nephrology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China ; [Zhou, Ying]Department of Nephrology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Physiology;Physiology (medical)
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17269
专题	基础医学院（机能实验教学中心）_病理学与病理生理学系附属第一医院_肾内科
通讯作者	Zheng, Chenfei; Zhou, Ying
作者单位	1.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Department of Internal Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Guanghua School of Stomatology,Sun Yat-sen University,Guangzhou,China; 4.Department of Nephrology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 附属第一医院_肾内科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Shentu, Yangping,Jiang, Huanchang,Liu, Xiaoyuan,et al. Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-alpha From Proteasomal Degradation[J]. FRONTIERS IN PHYSIOLOGY,2020,11:517912.
APA	Shentu, Yangping., Jiang, Huanchang., Liu, Xiaoyuan., Chen, Hao., Yang, Dicheng., ... & Zhou, Ying. (2020). Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-alpha From Proteasomal Degradation. FRONTIERS IN PHYSIOLOGY, 11, 517912.
MLA	Shentu, Yangping,et al."Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-alpha From Proteasomal Degradation".FRONTIERS IN PHYSIOLOGY 11(2020):517912.