Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

作者全名："Wang, Guoqing; Li, Xingran; Li, Na; Wang, Xiaotang; He, Siyuan; Li, Wanqian; Fan, Wei; Li, Ruonan; Liu, Jiangyi; Hou, Shengping"

作者地址："[Wang, Guoqing; Li, Xingran; Wang, Xiaotang; He, Siyuan; Li, Wanqian; Fan, Wei; Li, Ruonan; Liu, Jiangyi; Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wang, Guoqing; Li, Xingran; Wang, Xiaotang; He, Siyuan; Li, Wanqian; Fan, Wei; Li, Ruonan; Liu, Jiangyi; Hou, Shengping] Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Wang, Guoqing; Li, Xingran; Wang, Xiaotang; He, Siyuan; Li, Wanqian; Fan, Wei; Li, Ruonan; Liu, Jiangyi; Hou, Shengping] Chongqing Eye Inst, Chongqing, Peoples R China; [Wang, Guoqing; Li, Xingran; Wang, Xiaotang; He, Siyuan; Li, Wanqian; Fan, Wei; Li, Ruonan; Liu, Jiangyi; Hou, Shengping] Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Chongqing, Peoples R China; [Li, Na] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China"

通信作者："Hou, SP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：REDOX BIOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000794034100003

JCR分区：Q1

影响因子：11.4

年份：2022

卷号：52

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Icariin; Uveitis; PRDX3; Microglia; M1 phenotype; M2 phenotype

摘要："Uveitis causes blindness and critical visual impairment in people of all ages, and retinal microglia participate in uveitis progression. Unfortunately, effective treatment is deficient. Icariin (ICA) is a bioactive monomer derived from Epimedium. However, the role of ICA in uveitis remains elusive. Our study indicated that ICA alleviated intraocular inflammation in vivo. Further results showed the proinflammatory M1 microglia could be transferred to anti-inflammatory M2 microglia by ICA in the retina and HMC3 cells. However, the direct pharmacological target of ICA is unknown, to this end, proteome microarrays and molecular simulations were used to identify the molecular targets of ICA. Data showed that ICA binds to peroxiredoxin-3 (PRDX3), increasing PRDX3 protein expression in both a time-and a concentration-dependent manner and promoting the subsequent elimination of H2O2. In addition, GPX4/SLC7A11/ACSL4 pathways were activated accompanied by PRDX3 activation. Func-tional tests demonstrated that ICA-derived protection is afforded through targeting PRDX3. First, ICA-shifted microglial M1/M2 phenotypic polarization was no longer detected by blocking PRDX3 both in vivo and in vitro. Next, ICA-activated GPX4/SLC7A11/ACSL4 pathways and downregulated H(2)O(2 & nbsp;)production were also reversed via inhibiting PRDX3 both in vivo and in vitro. Finally, ICA-elicited positive effects on intraocular inflammation were eliminated in PRDX3-deficient retina from experimental autoimmune uveitis (EAU) mice. Taking together, ICA-derived PRDX3 activation has therapeutic potential for uveitis, which might be associated with modulating microglial M1/M2 phenotypic polarization."

基金机构："National Natural Science Foundation Project of China [81873678, 82070951]; Innovative Research Group Project of Chongqing Education Commission [CXQT19015]; Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0120]; Plan of Overseas Study of Chongqing [cx2018010]; National Key Clinical Specialties Construction Program of China (CSTC) [2008CA5003]; Natural Science Foundation Project of Chongqing Medical University [W0047]"

基金资助正文："This work was supported by National Natural Science Foundation Project of China (81873678, 82070951), the Innovative Research Group Project of Chongqing Education Commission (CXQT19015), the Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0120), the innovation supporting Plan of Overseas Study of Chongqing (cx2018010), National Key Clinical Specialties Construction Program of China, Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003),& nbsp;& nbsp;Natural Science Foundation Project of Chongqing Medical University (W0047)."