Department of Biomedicine, Health Faculty, Aarhus University, DK-8000 Aarhus C, Denmark.
Department of Clinical Medicine, Health Faculty, Aarhus University, DK-8200 Aarhus N, Denmark.
Int J Mol Sci. 2024 Feb 5;25(3):1904. doi: 10.3390/ijms25031904.
The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst-lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical targeting protein Syntaxin-3 also immunolocalized to the apical domain of cyst-lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Thus, no deviations from the typical epithelial distribution of basic cell polarity proteins were observed in the cysts from the six patients. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst-lining epithelia in polycystic kidney disease.
多囊肾病的主要特征是形成多个充满液体的肾囊肿。在囊壁衬里上皮细胞的顶膜中发现定位错误的钠钾泵(Na,K-ATPase),这暗示了极性反转可能是液体分泌的原因之一。囊中的顶端 Na,K-ATPase 仍然是一个有争议的话题。我们通过免疫组织化学方法,在 6 名接受肾切除术的多囊肾病患者的肾脏组织中,研究了 Na,K-ATPase 的定位,并评估了囊壁衬里上皮的顶-基底极性。Na,K-ATPaseα1 亚基通常位于所有免疫反应性囊肿的基底外侧膜上。Crumb 和 Partitioning defective(Par)复合物的蛋白定位于囊上皮细胞的顶膜域。顶端靶向蛋白 Syntaxin-3 也免疫定位于囊衬上皮细胞的顶端域。基底外侧 Scribble 复合物的蛋白定位于囊肿的基底外侧域。因此,在来自 6 名患者的囊肿中,没有观察到基本细胞极性蛋白的典型上皮分布出现偏差。此外,我们证实囊肿可以源自任何具有保留极性的管状段。总之,我们没有发现多囊肾病中囊壁衬里上皮的顶-基底极性反转的证据。