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Hippo/Wnt/LPA/TGF-β 信号通路的相互调控及其在青光眼发病机制中的作用(综述)。

Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review).

机构信息

Department of Biomedical Engineering, Medical School of University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.

Institute of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.

出版信息

Int J Mol Med. 2018 Mar;41(3):1201-1212. doi: 10.3892/ijmm.2017.3352. Epub 2017 Dec 29.

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide and there is no effective treatment thus far. The trabecular meshwork has been identified as the major pathological area involved. Certain signaling pathways in the trabecular meshwork, including the Wnt, lysophosphatidic acid and transforming growth factor‑β pathways, have been identified as novel therapeutic targets in glaucoma treatment. Meanwhile, it has been reported that key proteins in these pathways, particularly the primary transcription regulator Yes‑associated protein (YAP) and transcriptional co‑activator with PDZ‑binding motif (TAZ), exhibit interactions with the Hippo pathway. The Hippo pathway, which was first identified in Drosophila, has drawn great focus with regard to various aspects of studies in recent years. One role of the Hippo pathway in the regulation of organ size was indicated by more recent evidence. Defining the relevant physiological function of the Hippo pathway has proven to be extremely complicated. Studies have ascribed a role for the Hippo pathway in an overwhelming number of processes, including cell proliferation, cell death and cell differentiation. Therefore, the present review aimed to unravel the roles of YAP and TAZ in the Hippo pathway and the pathogenesis of glaucoma. Furthermore, a new and creative study for the treatment of glaucoma is provided.

摘要

青光眼是全球导致不可逆性失明的主要原因,目前尚无有效的治疗方法。小梁网已被确定为主要的病变部位。包括 Wnt、溶血磷脂酸和转化生长因子-β在内的某些小梁网信号通路已被确定为青光眼治疗的新的治疗靶点。同时,据报道,这些通路中的关键蛋白,特别是主要转录调节因子 Yes 相关蛋白(YAP)和与 PDZ 结合基序的转录共激活因子(TAZ),与 Hippo 通路相互作用。Hippo 通路最初在果蝇中被发现,近年来在各个研究领域引起了广泛关注。最近的证据表明 Hippo 通路在调节器官大小方面发挥作用。定义 Hippo 通路的相关生理功能被证明是极其复杂的。研究表明 Hippo 通路在包括细胞增殖、细胞死亡和细胞分化在内的大量过程中发挥作用。因此,本综述旨在阐明 YAP 和 TAZ 在 Hippo 通路和青光眼发病机制中的作用。此外,还提供了一种治疗青光眼的新的有创意的研究。

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