Genetic or siRNA inhibition of MBD2 attenuates the UUO- and I/R-induced renal fibrosis via downregulation of EGR1.
Genetic or siRNA inhibition of MBD2 attenuates the UUO- and I/R-induced renal fibrosis via downregulation of EGR1.
复制标题
MBD2 的遗传或 siRNA 抑制通过下调 EGR1 减轻 UUO 和 I/R 诱导的肾纤维化
DOI：
10.1016/j.omtn.2022.02.015
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发表时间：
2022-06-14
期刊：
影响因子：
--
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Ai K;Li X;Zhang P;Pan J;Li H;He Z;Zhang H;Yi L;Kang Y;Wang Y;Chen J;Li Y;Xiang X;Chai X;Zhang D
DNA甲基化在肾纤维化的进展中起着关键作用在波士顿大学小鼠代理管中由TGF-β1诱导（BUMPT）细胞，并更新了表达EGR1，以促进鼠类NIH 3T3的成纤维细胞中的ECM产生。通过下调Egr1通过纤连蛋白（FN），IV，IV，α-SMA和EGR1的下调证明了MBD2-SIRNA。通过下调EGR1的OSIS，这可能是治疗的靶标纤维化肾脏疾病。
我们验证了MBD2介导的TGF-β1诱导的ECM产生，并诱导EGR1促进鼠类胚胎NIH 3T3成纤维细胞的ECM产生。 - 和I/R诱导的肾纤维化。
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-β1 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, α-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. We verified that MBD2 mediated TGF-β1-induced ECM production by BUMPT cells and induced EGR1 to promote ECM production by murine embryonic NIH 3T3 fibroblasts. In vivo, PT-MBD2-KO attenuated UUO- and I/R-induced renal tubulointerstitial fibrosis via downregulation of EGR1. Injection of MBD2-siRNA attenuated the UUO- and I/R-induced renal fibrosis.
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G0/G1开关2的抑制可改善慢性肾脏疾病的肾脏炎症。
影响因子：
11.1
作者：
Matsunaga N;Ikeda E;Kakimoto K;Watanabe M;Shindo N;Tsuruta A;Ikeyama H;Hamamura K;Higashi K;Yamashita T;Kondo H;Yoshida Y;Matsuda M;Ogino T;Tokushige K;Itcho K;Furuichi Y;Nakao T;Yasuda K;Doi A;Amamoto T;Aramaki H;Tsuda M;Inoue K;Ojida A;Koyanagi S;Ohdo S
通讯作者：
Ohdo S
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
MBD2 通过影响 IRF4 表达来调节 Th17 细胞分化和实验性严重哮喘
影响因子：
4.6
作者：
Jia A;Wang Y;Sun W;Xiao B;Wei Y;Qiu L;Mu L;Xu L;Li J;Zhang X;Liu D;Peng C;Zhang D;Xiang X
通讯作者：
Xiang X
影响因子：
3.7
作者：
Dahal, Bibha;Lin, Shih-Chao;Kehn-Hall, Kylene
通讯作者：
Kehn-Hall, Kylene
DOI：
10.1016/s0169-328x(03)00047-0
发表时间：
2003-04-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Nakashima, A;Ota, A;Sabban, EL
通讯作者：
Sabban, EL