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Name pinyin
GENG Yiqing
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0710 生物学
Subject category of dissertation
07 理学
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肾脏是最重要的代谢器官之一,肾脏疾病困扰着数百万人,给全球公共医疗费用带来巨大负担。掌握预防肾小球疾病的潜在治疗靶点具有重要临床意义。CH-ILKBPα-parvin)是一种粘着斑蛋白,可调节多种生物学功能如细胞骨架。然而,关于CH-ILKBP在肾小球疾病中的作用知之甚少。为研究CH-ILKBP在生理条件下维持足细胞结构和功能的功能,利用Cre-LoxP系统在足细胞中条件性敲除CH-ILKBP基因,生成小鼠模型(CH-ILKBPNphs2 cKO)。足细胞缺失CH-ILKBP导致小鼠大量蛋白尿和肾衰竭。组织学上,在CH-ILKBPNphs2 cKO小鼠中观察到典型的肾脏损伤,包括肾小管空强化,蛋白类物质沉积和肾小球硬化。在机制方面,我们确定了一种关键的细胞连接蛋白ZO-1CH-ILKBP的相互作用。足细胞中CH-ILKBP的缺失导致ZO-1蛋白水平明显降低,同时细胞骨架的肌动蛋白纤维组织结构异常、裂隙隔膜表达异常和足细胞过滤能力受损。在CH-ILKBP缺陷的足细胞中恢复CH-ILKBPZO-1可有效减轻体内和体外由CH-ILKBP缺失引起的足细胞损伤。总的来说,我们的发现揭示了一个由CH-ILKBPZO-1组成的新的信号通路,在维持足细胞稳态中起重要作用。

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耿伊清. CH-ILKBP在调控足细胞结构和功能稳态中的作用机制研究[D]. 深圳. 南方科技大学,2022.
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