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结缔组织生长因子:在小梁网重塑和眼压降低中的作用。

Connective tissue growth factor: Role in trabecular meshwork remodeling and intraocular pressure lowering.

机构信息

Institute of Medical Molecular Biotechnology (IMMB), Universiti Teknologi MARA (UiTM), 47000 Sungai Buloh, Malaysia.

Department of Pharmacology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), 47000 Sungai Buloh, Malaysia.

出版信息

Exp Biol Med (Maywood). 2023 Aug;248(16):1425-1436. doi: 10.1177/15353702231199466. Epub 2023 Oct 24.

Abstract

Connective tissue growth factor (CTGF) is a distinct signaling molecule modulating many physiological and pathophysiological processes. This protein is upregulated in numerous fibrotic diseases that involve extracellular matrix (ECM) remodeling. It mediates the downstream effects of transforming growth factor beta (TGF-β) and is regulated via TGF-β SMAD-dependent and SMAD-independent signaling routes. Targeting CTGF instead of its upstream regulator TGF-β avoids the consequences of interfering with the pleotropic effects of TGF-β. Both CTGF and its upstream mediator, TGF-β, have been linked with the pathophysiology of glaucomatous optic neuropathy due to their involvement in the regulation of ECM homeostasis. The excessive expression of these growth factors is associated with glaucoma pathogenesis via elevation of the intraocular pressure (IOP), the most important risk factor for glaucoma. The raised in the IOP is due to dysregulation of ECM turnover resulting in excessive ECM deposition at the site of aqueous humor outflow. It is therefore believed that CTGF could be a potential therapeutic target in glaucoma therapy. This review highlights the CTGF biology and structure, its regulation and signaling, its association with the pathophysiology of glaucoma, and its potential role as a therapeutic target in glaucoma management.

摘要

结缔组织生长因子(CTGF)是一种独特的信号分子,调节许多生理和病理生理过程。该蛋白在涉及细胞外基质(ECM)重塑的许多纤维化疾病中上调。它介导转化生长因子β(TGF-β)的下游效应,并通过 TGF-β SMAD 依赖性和 SMAD 非依赖性信号通路进行调节。靶向 CTGF 而不是其上游调节剂 TGF-β 可以避免干扰 TGF-β 的多效性作用的后果。CTGF 及其上游介质 TGF-β 都与青光眼性视神经病变的病理生理学有关,因为它们参与 ECM 动态平衡的调节。这些生长因子的过度表达与青光眼的发病机制有关,其通过升高眼压(IOP),这是青光眼最重要的危险因素。IOP 的升高是由于 ECM 周转率的失调导致房水流出部位的 ECM 过度沉积。因此,CTGF 可能是青光眼治疗的一个潜在治疗靶点。这篇综述强调了 CTGF 的生物学和结构、其调节和信号转导、与青光眼病理生理学的关联,以及其作为青光眼管理治疗靶点的潜在作用。

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本文引用的文献

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Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery.结缔组织生长因子:从分子认识到药物发现
Front Cell Dev Biol. 2020 Oct 29;8:593269. doi: 10.3389/fcell.2020.593269. eCollection 2020.

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