Gevaert Thomas, Ridder Dirk De, Vanstreels Els, Daelemans Dirk, Everaerts Wouter, Aa Frank Van Der, Pintelon Isabel, Timmermans Jean-Pierre, Roskams Tania, Steiner Clara, Neuhaus Jochen
Laboratory of Experimental Urology, Organ Systems, KU Leuven, Leuven, Belgium.
Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
J Cell Mol Med. 2017 Jun;21(6):1206-1216. doi: 10.1111/jcmm.13054. Epub 2016 Dec 20.
The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT ICC are present in bladder. In this perspective, functional concepts of KIT ICC being involved in sensory and/or motor aspects of bladder physiology should be revised.
长期以来,人们一直认为肥大/干细胞生长因子受体KIT是膀胱中Cajal间质细胞(ICC)的特异性标志物,具有潜在的可药物作用前景。然而,近年来一些作者对膀胱中KIT⁺ ICC的存在提出了质疑。因此,本研究的目的是试图澄清关于人类、大鼠、小鼠和豚鼠膀胱中KIT表达的相互矛盾的报道,并阐明抗体相关问题和种间差异在这一问题上可能发挥的作用。从人类、大鼠、小鼠和豚鼠的膀胱切除术中获取新鲜样本,并进行单/双免疫组织化学/免疫荧光处理。使用针对KIT、肥大细胞类胰蛋白酶(MCT)、anoctamin-1(ANO1)和波形蛋白的特异性抗体来鉴定表达KIT的细胞类型。肠道(空肠)组织用作外部抗体对照。我们的结果显示,在人类、大鼠、小鼠和豚鼠膀胱中,KIT表达于肥大细胞而非ICC。平行免疫组织化学显示,在人类、大鼠、小鼠和豚鼠肠道中,KIT表达于ICC,这证实了KIT抗体克隆的选择性。总之,我们已经表明,人类、大鼠、小鼠和豚鼠膀胱中的KIT⁺细胞是肥大细胞而非ICC。本报告很重要,因为它反对膀胱中存在KIT⁺ ICC的观点。从这个角度来看,KIT⁺ ICC参与膀胱生理感觉和/或运动方面的功能概念应该被修正。