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Wnt信号通路影响角膜缘上皮干细胞干性机制的研究进展
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Abstract:
与其他组织的干细胞一样,周围微环境或角膜缘微环境严格支持和调节着LSCs的功能行为。角膜缘微环境具有独特的特征和成分,包括间充质细胞、免疫细胞、黑色素细胞、血管细胞、细胞外基质和信号分子(例如生长因子和细胞因子)。此外,该微环境包含各种信号通路的微妙平衡,包括Wnt、Notch、BMP、Shh、YAP和TGFβ。这些通路的激活或抑制通常取决于LSCs与微环境细胞和细胞外基质之间的相互作用。Wnt信号通路极大地促进了LSCs的体外自我更新能力。对LSCs或它们的生态微环境的损伤会导致角膜缘干细胞功能不全(LSCD)。了解LSCs在体外和体内的分子调控机制将大大有助于LSCD治疗的改进。本文重点综合了当前关于影响LSCs功能的微环境相关Wnt信号通路的文献。未来LSCD治疗的发展应考虑所有这些微环境因素,以改善LSCD人群的长期疗效。
Like the stem cells in other tissues, the surrounding microenvironment or limbal niche strictly supports and regulates the functional behaviors of LSCs. The limbal niche has unique characteristics and components, including mesenchymal cells, immune cells, melanocytes, vascular cells, extracellular matrix and signaling molecules (e.g., growth factors and cytokines). In addition, this niche contains a fine balance of various signaling pathways, including Wnt, Notch, BMP, Shh, YAP, and TGFβ. The activation or inhibition of these pathways usually depends on the interactions between LSCs and niche cells and extracellular matrix. The Wnt pathway greatly promotes the in vitro self-renewal ability of LSCs. Damage to LSCs or their ecological niches leads to corneal limbal stem cell deficiency (LSCD). The improvement of LSCD treatment will greatly benefit from understanding the molecular regulation of LSCs in vitro and in vivo. This review focuses on synthesizing current literature on niche related Wnt signaling pathways that affect LSC function. The future development of LSCD treatment should consider all these niche factors to improve the long-term recovery of the LSCD population.
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