Crosstalk between transforming growth factor β-2 and Autotaxin in trabecular meshwork and different subtypes of glaucoma.
Crosstalk between transforming growth factor β-2 and Autotaxin in trabecular meshwork and different subtypes of glaucoma.
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DOI：
10.1186/s12929-021-00745-3
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发表时间：
2021-06-17
影响因子：
11
通讯作者：
Aihara M
中科院分区：
文献类型：
--
作者：
Igarashi N;Honjo M;Yamagishi R;Kurano M;Yatomi Y;Igarashi K;Kaburaki T;Aihara M
房水中转化生长因子-β-2的升高与原发性开角型青光眼的小梁网纤维化和眼压调节有关，而在继发性开角型青光眼中，转化生长因子-β-2的表达下调。由于自体趋化蛋白(ATX)在SOAG中表达上调，我们研究了这些介体之间的关系和转导信号相互作用。用双点免疫酶法测定急性肝炎患者的ATX水平，用Bio-Plex Pro转化生长因子-β法测定转化生长因子-β水平。用核糖核酸显微镜检测ATX和转化生长因子-β-2在人眼组织中的表达。体外实验研究转化生长因子-ATX-2的反式信号转导是否调节β的表达。β-ATX2/ATX比值在对照组和POAG组明显高于SOAG组，且与眼压呈负相关。β-2和ATX在睫状体(CB)和TM均呈阳性表达，但ATX的表达在对照组明显增强。在HTM细胞中，转化生长因子-β-2以浓度依赖的方式调节ATx的表达。反之，ATX还可诱导转化生长因子-β-1、转化生长因子-β-2和TGFB1表达上调，Smad敏感启动子激活，纤维化标志物表达上调，这种上调可被转化生长因子-β和ATX抑制。转化生长因子-β-2的反式信号调节ATx的表达，从而诱导转化生长因子-β表达上调，S或纤维化。转化生长因子-ATX-2反式信号转导能有效地调节β转录和信号转导，这可能反映了这些介质在青光眼亚型中的不同分布。试验注册这项前瞻性观察性研究得到了东京大学机构审查委员会的批准，并在日本大学医院医学信息网络临床试验登记处注册(ID：UMIN000027137)。所有研究程序都符合《赫尔辛基宣言》。每名患者均获得书面知情同意。网上版载有补充材料，可在10.1186/s12929-021-00745-3查阅。
Elevated transforming growth factor (TGF)-β2 in aqueous humor (AH) has been suggested to contribute to trabecular meshwork (TM) fibrosis and intraocular pressure (IOP) regulation in primary open-angle glaucoma (POAG), but TGF-β2 is downregulated in secondary open-angle glaucoma (SOAG). Because autotaxin (ATX) is upregulated in SOAG, we investigated the relationships and trans-signaling interactions of these mediators. The level of ATX in AH was determined using a two-site immunoenzymetric assay, and TGF-β levels were measured using the Bio-Plex Pro TGF-β Assay. RNA scope was used to assess the expression of ATX and TGF-β2 in human’s eye specimen. And in vitro studies were performed using hTM cells to explore if trans-signaling of TGF-β2 regulates ATX expressions. TGF-β2/ATX ratio was significantly high in AH of control or POAG compared with SOAG, and negatively correlated with IOP. RNA scope revelated positive expressions of both TGF-β2 and ATX in ciliary body (CB) and TM in control, but ATX expressions was significantly enhanced in SOAG. In hTM cells, ATX expressions were regulated by TGF-β2 with concentration-dependent manner. In counter, ATX also induced TGF-β1, TGF-β2 and TGFBI upregulations and activation of the Smad-sensitive promoter, as well as upregulation of fibrotic markers, and these upregulation was significantly suppressed by both TGF-β and ATX inhibition. Trans-signaling of TGF-β2 regulates ATX expressions and thereby induced upregulations of TGF-βs or fibrosis of hTM. TGF-β2 trans-signaling potently regulate ATX transcription and signaling in hTM cells, which may reflect different profile of these mediators in glaucoma subtypes. Trial Registration This prospective observational study was approved by the Institutional Review Board of the University of Tokyo and was registered with the University Hospital Medical Information Network Clinical Trials Registry of Japan (ID: UMIN000027137). All study procedures conformed to the Declaration of Helsinki. Written informed consent was obtained from each patient. The online version contains supplementary material available at 10.1186/s12929-021-00745-3.
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对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
4.6
作者：
Igarashi N;Honjo M;Asaoka R;Kurano M;Yatomi Y;Igarashi K;Miyata K;Kaburaki T;Aihara M
通讯作者：
Aihara M
影响因子：
6.2
作者：
Bissey PA;Law JH;Bruce JP;Shi W;Renoult A;Chua MLK;Yip KW;Liu FF
通讯作者：
Liu FF
DOI：
10.1007/s004170000252
发表时间：
2001-03-01
影响因子：
2.7
作者：
Picht, G;Welge-Luessen, U;Lütjen-Drecoll, E
通讯作者：
Lütjen-Drecoll, E
影响因子：
6
作者：
Geng, Hui;Lan, Rongpei;Venkatachalam, Manjeri A.
通讯作者：
Venkatachalam, Manjeri A.