Small-molecule inhibition of Wnt signaling abrogates dexamethasone-induced phenotype of primary human trabecular meshwork cells.
Small-molecule inhibition of Wnt signaling abrogates dexamethasone-induced phenotype of primary human trabecular meshwork cells.
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DOI：
10.1016/j.yexcr.2017.05.009
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发表时间：
2017-08-01
影响因子：
3.7
通讯作者：
Zheng JJ
中科院分区：
文献类型：
--
作者：
Ahadome SD;Zhang C;Tannous E;Shen J;Zheng JJ
小梁网细胞是小梁网结构的调控细胞。当这些细胞的功能受损时，TM的结构就会受到干扰，这通常会导致高眼压增高。高眼压是类固醇性青光眼最重要的危险因素。地塞米松（Dex）诱导的TM细胞表型被广泛用作模型系统，以深入了解青光眼TM损伤的机制。在本研究中，为了评估异常Wnt信号在类固醇性青光眼中的可能作用，我们分析了小分子Wnt信号调节剂对dex诱导的人TM细胞细胞外基质蛋白表达的影响。虽然dex处理的TM细胞显示胶原和纤维连接蛋白表达增加，但我们发现Wnt信号抑制剂3235-0367抑制了这些dex诱导的作用。因此，我们提出Wnt信号在dex介导的TM细胞功能损伤中起重要作用。此外，使用小分子Wnt信号抑制剂治疗TM细胞可能为我们提供一个恢复类固醇性青光眼TM组织的机会。
Trabecular meshwork (TM) cells are the governing regulators of the TM structure. When the functionality of these cells is impaired, the structure of the TM is perturbed, which often results in increased ocular hypertension. High intraocular pressure is the most significant risk factor for steroid-induced glaucoma. Dexamethasone (Dex) induced phenotype of TM cells is widely utilized as a model system to gain insight into mechanisms underlying damaged TM in glaucoma. In this study, to assess the possible role of the abnormal Wnt signaling in steroid-induced glaucoma, we analyzed the effects of small-molecule Wnt signaling modulators on Dex-induced expression extracellular matrix proteins of primary human TM cells. While Dex-treated TM cells exhibited increased collagen and fibronectin expression, we found that Wnt signaling inhibitor 3235-0367 suppressed these Dex-induced effects. We therefore propose that Wnt signaling plays an important role in Dex-mediated impairment of TM cell functions. Moreover, the use of small molecule Wnt signaling inhibitors to treat TM cells may provide us an opportunity of restoring TM tissue in steroid-induced glaucoma.
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DOI：
10.1074/jbc.m115.673202
发表时间：
2015-12-18
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lee HJ;Bao J;Miller A;Zhang C;Wu J;Baday YC;Guibao C;Li L;Wu D;Zheng JJ
通讯作者：
Zheng JJ
影响因子：
3.4
作者：
Keller, Kate E.;Aga, Mini;Bradley, John M.;Kelley, Mary J.;Acott, Ted S.
通讯作者：
Acott, Ted S.
影响因子：
5.3
作者：
Lustig, B;Jerchow, B;Behrens, J
通讯作者：
Behrens, J
影响因子：
3.4
作者：
Faralli, Jennifer A.;Clark, Ross W.;Filla, Mark S.;Peters, Donna M.
通讯作者：
Peters, Donna M.
影响因子：
3.4
作者：
Junglas, Benjamin;Yu, Alice H. L.;Fuchshofer, Rudolf
通讯作者：
Fuchshofer, Rudolf