Spatiotemporal distribution of Wnt signaling pathway markers in human congenital anomalies of kidney and urinary tract

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica Pub Date : 2025-02-04 DOI:10.1016/j.acthis.2025.152235

Ilija Perutina , Nela Kelam , Mirko Maglica , Anita Racetin , Azer Rizikalo , Natalija Filipović , Ivana Kuzmić Prusac , Marko Bošnjak , Josip Mišković , Boris Kablar , Nasrollah Ghahrani , Katarina Vukojević

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引用次数: 0

Abstract

This study aimed to investigate the spatiotemporal expression patterns of key markers involved in regulating the canonical and non-canonical Wnt pathway during human fetal kidney development, comparing healthy (CTRL) and congenital anomalies of the kidney and urinary tract (CAKUT) affected kidneys. Human fetal kidneys, ranging from the 18th to the 38th developmental weeks, including various CAKUT phenotypes (horseshoe, dysplastic, duplex and hypoplastic), underwent double immunofluorescence microscopy analysis following antibody staining. Immunoreactivity levels were quantified in different kidney structures, and expression dynamics were assessed using linear and nonlinear regression modeling techniques. The study revealed a decrease in the overall protein expression of acetylated α-tubulin during normal kidney development, while the highest percentage of positive cells was observed in the horseshoe kidney (HK), thus disturbing microtubule composition in normal cell division and differentiation. Additionally, a continuous decrease of inversin-positive cells in hypoplastic (HYP) and duplex kidneys (UD), but the exponential growth of DVL-1 expression score in dysplastic kidneys (DYS) with developmental age, result in suppression of final kidney differentiation by continuous canonical Wnt signaling activation, thus supporting the essential role of the switch from canonical to non-canonical Wnt pathway in nephrogenesis. Furthermore β-catenin-positive cells in dysplastic and hypoplastic kidney exhibited the highest percentage of positive signal, with a decline in β-catenin positive cells over time in the control group, indicating disturbances in transition from canonical to non-canonical Wnt pathway in CAKUT-affected kidneys. The findings suggest that the crosstalk between canonical and non-canonical Wnt signaling pathways is crucial for normal nephrogenesis, highlighting their potential roles in normal and dysfunctional kidney development.

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Wnt信号通路标志物在人先天性肾、尿路异常中的时空分布

本研究旨在探讨人类胎儿肾脏发育过程中参与调节典型和非典型Wnt通路的关键标志物的时空表达模式，并比较健康（CTRL）和先天性肾尿路异常（CAKUT）肾脏的影响。在抗体染色后，采用双免疫荧光显微镜对发育第18至38周的人胎儿肾脏进行分析，包括各种CAKUT表型（马蹄型、发育不良型、双相型和发育不良型）。免疫反应性水平在不同的肾脏结构中被量化，并使用线性和非线性回归建模技术评估表达动态。研究发现，在正常肾脏发育过程中，乙酰化α-微管蛋白的总蛋白表达减少，而马蹄肾（HK）的阳性细胞比例最高，从而扰乱了正常细胞分裂和分化过程中的微管组成。此外，发育不良肾（HYP）和双肾（UD）中逆转录因子阳性细胞持续减少，而发育不良肾（DYS）中DVL-1表达评分随发育年龄呈指数增长，导致持续的典型Wnt信号激活抑制了最终的肾脏分化，从而支持了从典型到非典型Wnt通路转换在肾脏发生中的重要作用。此外，发育不良和发育不全肾脏中β-catenin阳性细胞的阳性信号比例最高，对照组中β-catenin阳性细胞随着时间的推移而下降，这表明cakut影响肾脏中从典型到非典型Wnt通路的转变受到干扰。研究结果表明，典型和非典型Wnt信号通路之间的串扰对正常肾脏形成至关重要，突出了它们在正常和功能障碍肾脏发育中的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta histochemica 生物-细胞生物学

CiteScore

4.60

自引率

4.00%

发文量

107

审稿时长

23 days

期刊介绍： Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted