Are testicular mast cells involved in the regulation of germ cells in man?
Are testicular mast cells involved in the regulation of germ cells in man?
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睾丸肥大细胞是否参与人类生殖细胞的调节？
DOI：
10.1111/j.2047-2927.2014.00227.x
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发表时间：
2014
期刊：
影响因子：
4.5
通讯作者：
Mayerhofer A
中科院分区：
文献类型：
--
作者：
Windschüttl S;Nettersheim D;Schlatt S;Huber A;Welter H;Schwarzer JU;Köhn FM;Schorle H;Mayerhofer A
蛋白酶激活受体-2 (PAR-2) 是原型肥大细胞产物类胰蛋白酶的受体。据报道，人类生发上皮细胞表达 PAR-2，但睾丸表达的确切细胞位点仍然未知。这引起了人们的兴趣，因为在患有不育症和不孕症的患者的生精小管壁中发现了表达类胰蛋白酶的肥大细胞。这个位置表明肥大细胞通过类胰蛋白酶可能能够影响生发上皮中表达 PAR-2 的细胞。为了探讨这些观点，我们使用睾丸石蜡包埋切片进行免疫组织化学分析。 PAR-2 阳性细胞主要是生精上皮的基底细胞，即精原细胞。有些对 GDNF (GFRalpha-1) 受体进行了染色，可能代表精原干细胞 (SSC)。由于无法检查真正的人类 SSC，我们转向表达 PAR-2 和干细胞标记物（包括 GFRalpha-1）的 TCam-2 精原细胞瘤细胞。 TCam-2 细胞通过增加细胞内 Ca2+ 水平对特定 PAR-2 激动剂 (SLIGKV) 的刺激做出强烈反应。重组类胰蛋白酶和胰蛋白酶（而非对照肽 (VKGILS)）引起了这种反应，这表明 PAR-2 具有功能性。视频成像和 caspase 3/7 测定表明 SLIGKV 和类胰蛋白酶可防止 TCam-2 细胞的自发凋亡并增加增殖。 PAR-2 激活后，多能性标记物 OCT3/4 的表达没有变化，表明干细胞样特征没有改变。此外，还检查了人类生殖细胞癌。一部分精原细胞瘤和原位癌样本表达 PAR-2，表明存在未知的亚组。总的来说，在人类睾丸切片、生殖细胞癌中获得的描述性数据以及 TCam-2 细胞的功能结果表明肥大细胞衍生的类胰蛋白酶对人类生殖细胞具有营养作用。这可能与人类生殖细胞癌的亚型以及可能的 SSC 相关。这也提出了 PAR-2 激动剂可能有助于人类 SSC 体外增殖的可能性。
Protease activated receptor‐2 (PAR‐2) is the receptor for the prototype mast cell product tryptase. PAR‐2 expression by cells of the human germinal epithelium was reported, but the exact cellular sites of testicular expression remained unknown. That became of interest, because mast cells, expressing tryptase, were found in the walls of seminiferous tubules of patients suffering from sub‐ and infertility. This location suggested that mast cells via tryptase might be able to influence PAR‐2‐expressing cells in the germinal epithelium. To explore these points, we used testicular paraffin‐embedded sections for immunohistochemistry. PAR‐2‐positive cells were mostly basally located cells of the seminiferous epithelium, namely spermatogonia. Some stained for the receptor for GDNF (GFRalpha‐1), and possibly represent spermatogonial stem cells (SSCs). As true human SSCs could not be examined, we turned to TCam‐2 seminoma cells, expressing PAR‐2 and stem cell markers, including GFRalpha‐1. TCam‐2 cells robustly responded to stimulation with a specific PAR‐2 agonist (SLIGKV) by increased intracellular Ca2+levels. Recombinant tryptase and trypsin, but not a control peptide (VKGILS) evoked this response, implying functional PAR‐2. Video imaging and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous apoptosis and increased proliferation of TCam‐2 cells. The expression of the marker of pluripotency OCT3/4 was unchanged upon activation of PAR‐2, suggesting that the stem cell‐like character is not changed. Furthermore, human germ cell cancers were examined. A subset of seminoma and carcinoma in situ samples expressed PAR‐2, indicating that yet unknown subgroups exist. Collectively, the descriptive data obtained in human testicular sections, in germ cell cancers and the functional results in TCam‐2 cells imply a trophic role of mast cell‐derived tryptase for human germ cells. This may be relevant for subtypes of human germ cell cancers, and possibly SSCs. It also raises the possibility that PAR‐2 agonists might be useful for the in vitro propagation of human SSCs.
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影响因子：
6.7
作者：
H. Welter;F. Köhn;A. Mayerhofer
通讯作者：
A. Mayerhofer
影响因子：
6.1
作者：
Saller, S.;Kunz, L.;Mayerhofer, A.
通讯作者：
Mayerhofer, A.
影响因子：
3.2
作者：
Som A;Wen S;Tu SM
通讯作者：
Tu SM
影响因子：
3.7
作者：
Nettersheim D;Heukamp LC;Fronhoffs F;Grewe MJ;Haas N;Waha A;Honecker F;Waha A;Kristiansen G;Schorle H
通讯作者：
Schorle H
影响因子：
6.1
作者：
von Kopylow, Kathrein;Kirchhoff, Christiane;Spiess, Andrej-Nikolai
通讯作者：
Spiess, Andrej-Nikolai