METTL3 inhibits inflammation of retinal pigment epithelium cells by regulating NR2F1 in an m(6)A-dependent manner

作者全名："Meng, Jiayu; Liu, Xianyang; Tang, Shiyun; Liu, Yusen; Zhao, Chenyang; Zhou, Qian; Li, Na; Hou, Shengping"

作者地址："[Meng, Jiayu; Liu, Xianyang; Tang, Shiyun; Liu, Yusen; Zhao, Chenyang; Zhou, Qian; Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Meng, Jiayu; Liu, Xianyang; Tang, Shiyun; Liu, Yusen; Zhao, Chenyang; Zhou, Qian; Hou, Shengping] Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Meng, Jiayu; Liu, Xianyang; Tang, Shiyun; Liu, Yusen; Zhao, Chenyang; Zhou, Qian; Hou, Shengping] Natl Clin Res Ctr Ocular Dis, Ophthalmol, Chongqing Branch, Chongqing, Peoples R China; [Li, Na] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China"

通信作者："Hou, SP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China.; Hou, SP (通讯作者)，Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China.; Hou, SP (通讯作者)，Natl Clin Res Ctr Ocular Dis, Ophthalmol, Chongqing Branch, Chongqing, Peoples R China.; Li, N (通讯作者)，Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000836004600001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：METTL3; RPE; inflammation; M(6)A

摘要："N-6-metyladenosine (m(6)A) RNA methylation has been proven to be involved in diverse biological processes, but its potential roles in the development of lipopolysaccharide (LPS) induced retinal pigment epithelium (RPE) inflammation have not been revealed. In this study, we explored the effects and underlying mechanisms of methyltransferase-like 3 (METTL3) in LPS stimulated RPE cells. Proliferation of METTL3-silenced RPE cells was examined by Cell counting kit-8 (CCK8) and 5-Ethynyl-2 '-Deoxyuridine (Edu). Expression of tight junction proteins ZO-1 and Occludin, and secretion of inflammatory factors interleukins (IL)-1, 6 and 8 were detected by Western blotting or Enzyme-linked immunosorbent assay (ELISA). RNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing were used to analyze the target gene nuclear receptor subfamily 2 group F member 1 (NR2F1) of METTL3. Our results showed that both human RPE (hRPE) cells and ARPE19 cells exhibited inhibited proliferation, tight junction protein expression, and increased inflammatory factor secretion after METTL3 silencing. Mechanistically, we found that NR2F1, as a METTL3-methylated target gene, inhibits Occludin level and promotes IL-6 secretion of RPE cells in an m(6)A-dependent manner. Interestingly, NR2F1 deficiency reversed the decreased Occludin expression and increased IL-6 secretion in METTL3-defective RPE cells. In conclusion, our study revealed that METTL3 attenuates RPE cell inflammation by methylating NR2F1, suggesting the critical role of METTL3 in RPE cells."

基金机构："National Natural Science Foundation Project of China [82070951, 81873678]; Innovative Research Group Project of Chongqing Education Commission [CXQT19015]; Natural Science Foundation Project of Chongqing [cstc2019jcyjmsxmX0120]; Innovation Supporting Plan of Overseas Study of Chongqing [cx2018010]; Chongqing Education Commission [KJQN202000406]; Chongqing Branch of National Clinical Research Center for Ocular Diseases; Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [w0047]; National Key Clinical Specialties Construction Program of China"

基金资助正文："This study was supported by the National Natural Science Foundation Project of China (82070951 and 81873678); the Innovative Research Group Project of Chongqing Education Commission (CXQT19015); the Natural Science Foundation Project of Chongqing (cstc2019jcyjmsxmX0120); the Innovation Supporting Plan of Overseas Study of Chongqing (cx2018010); the Chongqing Education Commission (KJQN202000406); the National Key Clinical Specialties Construction Program of China, Chongqing Branch of National Clinical Research Center for Ocular Diseases; the Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003) and Program for Youth Innovation in Future Medicine, Chongqing Medical University (w0047)."