Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Šoltanska 2, 21000 Split, Croatia.
Department of Medical Genetics, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
Int J Mol Sci. 2021 Mar 28;22(7):3500. doi: 10.3390/ijms22073500.
The spatiotemporal expression of α-tubulin, inversin and dishevelled-1 (DVL-1) proteins associated with the Wnt-signaling pathway, and primary cilia morphology were analyzed in developing kidneys (14th-38th developmental weeks), healthy postnatal (1.5- and 7-years old) and pathologically changed human kidneys, including multicystic dysplastic kidneys (MCDK), focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome of the Finnish type (CNF). The analysis was performed by double immunofluorescence, electron microscopy, semiquantitative and statistical methods. Cytoplasmic co-expression of α-tubulin, inversin and DVL-1 was observed in the proximal convoluted tubules (pct), distal convoluted tubules (dct) and glomeruli (g) of analyzed tissues. During kidney development, the overall expression of α-tubulin, inversin and DVL-1 decreased, while in the postnatal period slightly increased. The highest expressions of α-tubulin and inversin characterized dct and g, while high DVL-1 characterized pct. α-tubulin, inversin and DVL-1 expression pattern in MCDK, FSGS and CNF kidneys significantly differed from the healthy control. Compared to healthy kidneys, pathologically changed kidneys had dysmorphic primary cilia. Different expression dynamics of α-tubulin, inversin and DVL-1 during kidney development could indicate that switch between the canonical and noncanonical Wnt-signaling is essential for normal kidney morphogenesis. In contrast, their disturbed expression in pathological kidneys might be associated with abnormal primary cilia, leading to chronic kidney diseases.
与 Wnt 信号通路相关的α-微管蛋白、内反转蛋白和 DVL-1 蛋白的时空表达以及初级纤毛形态在发育中的肾脏（第 14-38 周发育阶段）、健康的产后（1.5 岁和 7 岁）和病理性改变的人类肾脏中进行了分析，包括多囊性发育不良肾脏（MCDK）、局灶性节段性肾小球硬化症（FSGS）和芬兰型肾病综合征（CNF）。通过双重免疫荧光、电子显微镜、半定量和统计方法进行了分析。在分析的组织中，近端曲管（pct）、远端曲管（dct）和肾小球（g）中观察到α-微管蛋白、内反转蛋白和 DVL-1 的细胞质共表达。在肾脏发育过程中，α-微管蛋白、内反转蛋白和 DVL-1 的总体表达减少，而在产后阶段略有增加。α-微管蛋白和内反转蛋白的表达水平最高的是 dct 和 g，而 DVL-1 的表达水平最高的是 pct。MCDK、FSGS 和 CNF 肾脏中α-微管蛋白、内反转蛋白和 DVL-1 的表达模式与健康对照组明显不同。与健康肾脏相比，病理性改变的肾脏中的初级纤毛形态异常。在肾脏发育过程中，α-微管蛋白、内反转蛋白和 DVL-1 的表达动力学不同，这表明经典和非经典 Wnt 信号之间的转换对于正常肾脏形态发生是必不可少的。相反，它们在病理性肾脏中的异常表达可能与异常的初级纤毛有关，导致慢性肾脏疾病。
