随着对酸敏感离子通道(Acid-sensing ion channels,ASICs)研究的不断深入,其在临床相关疾病中的功能研究也逐渐受到重视。ASICs的功能异常与一系列临床疾病和症状密切相关,包括神经系统肿瘤、缺血性损伤、癫痫、疼痛以及亨廷顿氏症等。在细胞内正常的分布与定位是AISCs发挥其生理功能的前提,而多项研究已经确认,在正常生理的状态下,ASICs在细胞内具有相对固定的分布方式。换言之,正常的细胞内存在着可以对ASICs的分布进行调节的调控系统。目前也发现了包括PICK1、HSP70等与之相关的一系列物质分子。鉴于ASICs在人体诸多生理、病理过程中发挥重要作用,对ASICs功能异常的相关研究便成为了目前基础研究工作的重点之一。本文拟就ASICs在细胞内的分布定位及其转运调节机制作一综述,进而初步探讨其在临床应用中的前景。
Response gene to complement 32 （RGC-32） is a cell cycle regulator involved in the proliferation, differentiation and migration of cells and has also been implicated in angiogenesis. Here we show that RGC-32 expression in macrophages is induced by IL-4 and reduced by LPS, indicating a link between RGC-32 expression and M2 polarization. We demonstrated that the increased expression of RGC-32 is characteristic of alternatively activated macrophages, in which this protein suppresses the production of pro-inflammatory cytokine IL-6 and promotes the production of the anti-inflammatory mediator TGF-β. Consistent with in vitro data, tumor-associated macrophages （TAMs） express high levels of RGC-32, and this expression is induced by tumor-derived ascitic fluid in an M-CSF- and/or IL-4-dependent manner. Collectively, these results establish RGC-32 as a marker for M2 macrophage polarization and indicate that this protein is a potential target for cancer immunotherapy, targeting tumor-associated macrophages.
Background Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma （RCC） is a hypervascular tumor that reportedly increases the frequency of regulatory T cells （Tregs） in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. Methods Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4＋CD25highCD127low/- T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes （TILs） were determined by flow cytometry. The expression of vascular endothelial growth factor （VEGF） in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay （ELISA） kit. Microvessel density （MVD） was calculated on slides stained with CD34 antibody. Spearman＇s rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. Results Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC （P 〈0.05）. The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC （P 〈0.01）. In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage （P 〈0.05） and nuclear grade （P 〈0.01）. Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression （r=0.51, P 〈0.05）, as well as between frequencies of Tregs and MVD score （r=0.39, P 〈0.05）. Conclusions These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance u
