IL-22/IL-22RA1 Promotes Human Tenon's Capsule Fibroblasts Proliferation and Regulates Fibrosis Through STAT3 Signaling Pathway.

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-07-24 DOI:10.1089/jop.2023.0122
Yang Zhao, Xinyue Zhang, Xiaoyu Zhou, Baihua Chen, Xuanchu Duan
{"title":"IL-22/IL-22RA1 Promotes Human Tenon's Capsule Fibroblasts Proliferation and Regulates Fibrosis Through STAT3 Signaling Pathway.","authors":"Yang Zhao, Xinyue Zhang, Xiaoyu Zhou, Baihua Chen, Xuanchu Duan","doi":"10.1089/jop.2023.0122","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. <b><i>Method:</i></b> A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. <b><i>Results:</i></b> The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. <b><i>Conclusions:</i></b> The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"435-444"},"PeriodicalIF":1.9000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ocular Pharmacology and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jop.2023.0122","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. Method: A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. Results: The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. Conclusions: The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
IL-22/IL-22RA1 通过 STAT3 信号通路促进人腱鞘囊成纤维细胞增殖并调节纤维化。
目的:尽管现在人们已经明白,大多数抗青光眼手术失败的原因是滤过道瘢痕形成,但其根本机制仍有待阐明。本研究探讨了白细胞介素(IL)-22/IL-22受体α1(IL-22RA1)信号通路调节青光眼患者瘢痕形成的机制。研究方法本研究共纳入 31 例因瘢痕形成导致眼压无法控制而接受小梁切除手术的青光眼患者,以及 19 例斜视患者作为对照组。采用 ELISA 方法检测外周血中 IL-22 的含量。用患者血清孵育人腱鞘囊成纤维细胞(HTFs),并用 IL-22 抗体挽救 IL-22 对生物功能的影响。流式细胞术评估细胞周期分布,细胞计数试剂盒-8分析细胞增殖。结果酶联免疫吸附试验显示,青光眼患者血清中的 IL-22 水平明显高于健康组(29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL)。与患者血清培养后,人腱鞘成纤维细胞(HTFs)的增殖和活化得到促进。IL-22 通过直接结合 IL-22RA1 介导 HTFs 的生物功能。此外,转染 siR-IL-22RA1 或 IL-22RA1 基因后,HTFs 可显著抗纤维化或抗疤痕化。在 IL-22RA1 过表达组中引入信号转导和转录激活剂(STAT)3 抑制剂(BAY)后,IL-22 诱导的 HTF 增殖减少。此外,青光眼患者手术后 IL-22 表达水平升高。结论:IL-22/IL-22RA1IL-22/IL-22RA1/STAT3信号通路促进了成纤维细胞增殖和α-平滑肌肌动蛋白,可能调节了青光眼滤过道的纤维化。我们的研究结果为术后瘢痕的病理生理学提供了迄今为止尚未被证实的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
4.60
自引率
4.30%
发文量
72
审稿时长
1 months
期刊介绍: Journal of Ocular Pharmacology and Therapeutics is the only peer-reviewed journal that combines the fields of ophthalmology and pharmacology to enable optimal treatment and prevention of ocular diseases and disorders. The Journal delivers the latest discoveries in the pharmacokinetics and pharmacodynamics of therapeutics for the treatment of ophthalmic disorders. Journal of Ocular Pharmacology and Therapeutics coverage includes: Glaucoma Cataracts Retinal degeneration Ocular infection, trauma, and toxicology Ocular drug delivery and biotransformation Ocular pharmacotherapy/clinical trials Ocular inflammatory and immune disorders Gene and cell-based therapies Ocular metabolic disorders Ocular ischemia and blood flow Proliferative disorders of the eye Eyes on Drug Discovery - written by Gary D. Novack, PhD, featuring the latest updates on drug and device pipeline developments as well as policy/regulatory changes by the FDA.
期刊最新文献
Duration of Bare Sclera Pterygium Surgery Combined with Mitomycin C with and Without Tranexamic Acid: A Randomized Double-Blind Controlled Trial. Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension. Effects of Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study. Eyes on New Product Development. Neuritin 1 Drives Therapeutic Preservation of Retinal Ganglion Cells in an Ex Vivo Human Glaucoma Model.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1