MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.
MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.
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DOI：
10.21037/atm-22-982
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发表时间：
2022-03
影响因子：
--
通讯作者：
Ye, Lin
中科院分区：
文献类型：
--
作者：
Guo, Hui;Zhang, Yongxin;Liao, Zifang;Zhan, Wenzhu;Wang, Yuan;Peng, Yun;Yang, Meina;Ma, Xudai;Yin, Guogan;Ye, Lin
关键词：
过敏性结膜炎(AC)是由结膜对外界过敏原的超敏免疫反应引起的炎症。MicroRNA(MiRNA)miR-146a已被报道可抑制炎症的加剧。然而，miR-146a在AC中的潜在作用和机制尚未完全阐明。我们首先成功地建立了AC小鼠模型和AC细胞模型。采用逆转录定量聚合酶链式反应(RT-qPCR)检测miR-146a、FOXP3和同源域相互作用蛋白激酶3(HIPK3)的表达。用酶联免疫吸附分析试剂盒检测免疫球蛋白E、肿瘤坏死因子-α、白介素10、白介素4、转化生长因子-α的水平，用免疫印迹、免疫荧光或免疫组织化学方法检测相关蛋白的表达，用双荧光素酶报告基因检测miR-146a与HIPK3的相互作用，苏木精-伊红染色证实炎性细胞的浸润。我们的结果表明，在AC模型小鼠中miR-146a和FOXP3表达下调。同时，在转化生长因子-β诱导的胸腺细胞中，miR-146a过表达可上调FOXP3，抑制炎症反应。此外，我们的结果证明，HIPK3作为miR-146a的靶基因，可以逆转miR-146a介导的FOXP3上调和炎症抑制。此外，我们还发现miR-146a可以通过靶向HIPK3下调p-STAT3，并且STAT3的激活也可以逆转转化生长因子-β诱导的胸腺细胞中miR-146a介导的炎症抑制。更重要的是，miR-146a可以改善AC模型小鼠的炎症浸润，下调HIPK3和p-STAT3的表达。我们证实了miR-146a/HIPK3/STAT3轴可能的保护机制，miR-146a的减少可以加重AC的炎症反应。
Allergic conjunctivitis (AC) is an inflammation caused by a hypersensitive immune reaction of conjunctiva to external allergens. The microRNA (miRNA) miR-146a has been reported to suppress the exacerbation of inflammation. However, the underlying influence and mechanism of miR-146a in AC has not been completely elucidated. We first successfully established an AC mouse model and AC cell model. After each model was treated based on the experimental purposes, miR-146a, FOXP3, and homeodomain-interacting protein kinases 3 (HIPK3) expressions were estimated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The levels of immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were assessed using enzyme-linked immunosorbent assay (ELISA) kits; the related proteins were analyzed by western blot, immunofluorescence, or immunohistochemistry (IHC) assays; the interaction between miR-146a and HIPK3 were validated by a dual-luciferase reporter gene assay; and the inflammatory infiltration was certified by hematoxylin and eosin (H&E) staining. Our results indicated that miR-146a and FOXP3 were downregulated in AC model mice. Meanwhile, miR-146a overexpression could upregulate FOXP3 and inhibit inflammatory response in TGF-β-induced thymocytes. Besides, our results testified that HIPK3, as a target gene of miR-146a, could reverse miR-146a-mediated FOXP3 upregulation and inflammation inhibition. Moreover, we discovered that miR-146a could downregulate p-STAT3 by targeting HIPK3, and activation of STAT3 also could reverse miR-146a-mediated inflammation suppression in TGF-β-induced thymocytes. More importantly, miR-146a could ameliorate inflammatory infiltration and downregulate HIPK3 and p-STAT3 in AC model mice. We demonstrated a possible protective mechanism by the miR-146a/HIPK3/STAT3 axis, by which decrease of miR-146a could aggravate the inflammation of AC.
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影响因子：
5.1
作者：
Liu, Ben;Hou, Qiuyue;Han, Xuehua
通讯作者：
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影响因子：
12.4
作者：
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DOI：
10.29271/jcpsp.2020.11.1166
发表时间：
2020-11-01
影响因子：
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作者：
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通讯作者：
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影响因子：
4.3
作者：
Ding, Yuanyuan;Li, Chaomei;He, Langchong
通讯作者：
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影响因子：
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作者：
Berger, William E.;Granet, David B.;Kabat, Alan G.
通讯作者：
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