Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

中文翻译：

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人多囊性肾发育不良中 AKT 通路的高激活

多囊性肾发育不良是由未成熟肾小管异常后肾分化引起的肾脏先天性囊性异常。它被间充质环和包囊之间存在的未成熟间充质岛包围。PI3K-AKT-mTOR 信号通路是参与细胞生长、增殖、运动、存活和凋亡的关键调节剂。PI3K-AKT-mTOR 通路的激活导致许多癌症中肿瘤细胞的存活和增殖。本研究的目的是分析磷酸 AKT、磷酸 mTOR 和磷酸 70S6K 在肾脏发育和多囊性发育不良肾 (MCDK) 中的拓扑表达。为了评估磷酸-AKT（S473）、磷酸-mTOR和磷酸-70S6K的表达，通过免疫组织化学分析了总共17个从妊娠早期到晚期的发育年龄的胎儿肾脏和13例具有MCDK的病理性肾脏。 . Phospho-AKT 和 phospho-mTOR 在肾脏发育早期表达，并且以相同的方式表达来自输尿管芽的每个结构，例如集合管和尿路上皮。Phospho-p70S6K 早期在尿路上皮和肾小球系膜细胞中表达。后来，它们的表达随着时间的推移变得更具选择性，根据细胞增殖和分化的需要而有所不同。在 MCDK 中，磷酸化 AKT、磷酸化 mTOR 和磷酸化 70S6K 具有相同的特征：在囊性上皮、疏松间充质和原始管中的高细胞质表达。