Distribution and possible role of PDGF-AA and PDGFR-α in the gastrointestinal tract of adult guinea pigs

Distribution and possible role of PDGF-AA and PDGFR-α in the gastrointestinal tract of adult guinea pigs
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PDGF-AA和PDGFR-α在成年豚鼠胃肠道中的分布和可能的作用

DOI:
10.1007/s00428-010-0946-0
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发表时间:
2010-09-01
期刊:
影响因子:
3.5
通讯作者:
Zhou, Deshan
Zhou, Deshan
中科院分区:
医学3区
文献类型:
--
作者:
Chan, Fangxiao;Liu, Yong;Zhou, Deshan

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据报道,血小板衍生生长因子(PDGFs)及其受体(PDGFRs)的信号通路在小鼠肠道发育中起着关键作用。PDGFR-α基因在胃肠道间质瘤中的过表达表明,部分肿瘤细胞来源于PDGFR-α阳性细胞,但PDGFR-α在成年哺乳动物肠道中的更详细分布及其可能的作用尚不清楚。在本研究中,我们用免疫印迹和免疫组织化学方法检测了PDGFAA及其受体α在成年豚鼠胃肠道中的表达。PDGF-AA免疫反应阳性细胞主要分布于胃、小肠和大肠的粘膜上皮细胞。大肠纵肌层仅见少量PDGF-AA阳性细胞。相反,PDGFR-α阳性细胞广泛分布于整个胃肠道,包括固有层、肌层和浆膜下。免疫组织化学双标结果显示,PDGFR-α阳性细胞在肌层的分布与Cajal间质细胞(ICCs)相似,与ICCs和肠神经联系,而抗PDFR和Kit抗体未见双标细胞。Pdgfr-α阳性细胞也被波形蛋白单抗染色。根据双重染色和形态特征,我们认为PDGFR-α阳性细胞属于成纤维细胞的一个亚型。我们的结果不仅为了解PDGF/PDGFR信号通路在正常成年哺乳动物和肠道损伤修复过程中的功能提供了路线图,而且可能有助于在临床上了解GIST的生长发育。
It was reported that a signaling pathway of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) played a critical role in the developing gut of mice. Overexpression of the PDGFR-α gene in gastrointestinal stromal tumors (GISTs) indicated that parts of tumor cells originated from PDGFR-α-positive cells, but a more detailed distribution of PDGFR-α and possible role in the adult mammalian gut are still unclear. In the present study, we examined the expression of both PDGF-AA and its receptor PDGFR-α in the gastrointestinal (GI) tract of adult guinea pigs using western blotting and immunohistochemistry. PDGF-AA-immunoreactive cells were mainly distributed in the mucosal epithelium of the stomach, small intestine, and large intestine. Only a few PDGF-AA-positive cells were seen in the longitudinal muscle layer of the large intestine. In contrast, PDGFR-α-positive cells were widely distributed throughout the GI tract, including the lamina propria, muscular layer, and subserosa. Double staining showed that the distribution of the PDGFR-α-positive cells in the muscular layer were similar to those of the interstitial cells of Cajal (ICCs), and they were associated with ICCs and enteric nerves, but no double-labeled cells were observed by anti-PDGFR or Kit antibody. It was noted that PDGFR-α-positive cells were also stained with a vimentin monoclonal antibody. Based on the double staining and morphological features, we consider the PDGFR-α-positive cells belong to a subtype of fibroblast. Our results not only provide a roadmap for understanding the function of the PDGF/PDGFR signaling pathway in both normal adult mammals and during gut injury and repair but also might help in understanding the growth and development of GISTs in the clinic.