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人、豚鼠和猪膀胱间质细胞的免疫组织化学比较特征

Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

作者信息

Steiner Clara, Gevaert Thomas, Ganzer Roman, De Ridder Dirk, Neuhaus Jochen

机构信息

Department of Urology, Research Laboratories, University of Leipzig, Liebigstraße 19, Building C., 04103, Leipzig, Germany.

Organ Systems, Laboratory of Experimental Urology, KU Leuven, Leuven, Belgium.

出版信息

Histochem Cell Biol. 2018 May;149(5):491-501. doi: 10.1007/s00418-018-1655-z. Epub 2018 Feb 20.

Abstract

Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM/PDGFRα and ≥ 90% were VIM/TRPA1. In human and pig ≥ 74% of ULP ICs were VIM/αSMA, while in GP the percentage differed significantly with only 37% VIM/αSMA ICs. Additionally, over 90% of αSMA ICs were also TRPA1 and PDGFRα in human, GP and pig. In all three species, TRPA1 and PDGFRα ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

摘要

间质细胞(ICs)被认为在膀胱中发挥功能作用。动物模型常用于阐明膀胱生理学和病理生理学。然而,关于ICs的种间比较研究很少。因此,我们分析了人、豚鼠(GP)和猪的膀胱黏膜固有层上层(ULP)、黏膜固有层深层(DLP)和逼尿肌层(DET)中的ICs及其分布。通过免疫组织化学以及对间充质中间丝波形蛋白(VIM)、α平滑肌肌动蛋白(αSMA)、血小板衍生生长因子受体α(PDGFRα)和瞬时受体电位阳离子通道A1(TRPA1)进行三维共聚焦免疫荧光检查石蜡切片。使用Huygens软件对图像堆栈进行处理以进行分析;使用Fiji宏进行定量分析。通过VIM免疫反应性(不包括血管)鉴定ICs。在所有物种中,≥75%的ULP ICs为VIM/PDGFRα,≥90%为VIM/TRPA1。在人和猪中,≥74%的ULP ICs为VIM/αSMA,而在豚鼠中该百分比差异显著,只有37%的ICs为VIM/αSMA。此外,在人、豚鼠和猪中,超过90%的αSMA ICs也为TRPA1和PDGFRα。在所有三个物种中,TRPA1和PDGFRα ICs表明这些细胞在膀胱生理学中在传入信号传导过程和信号修饰方面发挥积极作用。我们假设豚鼠中αSMA阳性率的下降反映了膀胱组织学对较小膀胱尺寸的适应。在我们的实验中,猪膀胱被证明与人类膀胱高度可比,并且似乎比豚鼠更能为实验结果提供可靠的解释。

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