Genetic or siRNA inhibition of MBD2 attenuates the UUO- and I/R-induced renal fibrosis via downregulation of EGR1

被引：25

作者：

Ai, Kai ^{[1
,2
,3
]}

Li, Xiaozhou ^{[1
,2
]}

Zhang, Pan ^{[1
,2
,4
]}

Pan, Jian ^{[1
,2
]}

Li, Huiling ^{[5
]}

He, Zhibiao ^{[1
,2
]}

Zhang, Hongliang ^{[1
,2
]}

Yi, Lei ^{[3
]}

Kang, Ye ^{[3
]}

Wang, Yinhuai ^{[3
]}

Chen, Junxiang ^{[6
]}

Li, Yijian ^{[3
]}

Xiang, Xudong ^{[1
,2
]}

Chai, Xiangping ^{[1
,2
]}

Zhang, Dongshan ^{[1
,2
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Dept Emergency Med, Changsha 410011, Hunan, Peoples R China

[2] Cent South Univ, Xiangya Hosp 2, Emergency Med & Difficult Dis Inst, Changsha 410011, Hunan, Peoples R China

[3] Cent South Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Changsha 410011, Hunan, Peoples R China

[5] Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha 410011, Hunan, Peoples R China

[6] Cent South Univ, Xiangya Hosp 2, Dept Nephrol, Changsha 410011, Hunan, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2022年 / 28卷

基金：

中国国家自然科学基金;

关键词：

DNA METHYLATION; FIBROBLAST ACTIVATION; INTERSTITIAL FIBROSIS; SEPTIC AKI; KEY ROLE; GROWTH; INFLAMMATION; DEFICIENCY; EXPRESSION; DIFFERENTIATION;

D O I：

10.1016/j.omtn.2022.02.015

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

DNA methylation plays a pivotal role in the progression of renal fibrosis. Methyl-CpG-binding domain protein 2 (MBD2), a protein reader of methylation, is involved in the development of acute kidney injury (AKI) caused by vancomycin. However, the role and mechanism of action of MBD2 in renal remain unclear. In this study, MBD2 mediated extracellular matrix (ECM) production induced by TGF-beta 1 in Boston University mouse proximal tubule (BUMPT) cells,and upregulated the expression EGR1 to promote ECM production in murine embryonic NIH 3T3 fibroblasts. ChIP analysis demonstrated that MBD2 physically interacted with the promoter region of the CpG islands of EGR1 genes and then activated their expression by inducing hypomethylation of the promoter region. In vivo, PT-MBD2-KO attenuated unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis via downregulation of EGR1, which was demonstrated by the downregulation of fibronectin (FN), collagen I and IV, alpha-SMA, and EGR1. Injection of MBD2-siRNA attenuated the UUO- and I/R-induced renal fibrosis. Those molecular changes were verified by biopsies from patients with obstructive nephropathy (OB). These data collectively demonstrated that inhibition of MBD2 reduces renal fibrosis via downregulating EGR1, which could be a target for treatment of fibrotic kidney disease.

引用

页码：77 / 86

页数：10

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