PDF(Pubmed)
Abstract：
The lymphatic network of capillaries and collecting vessels ensures tissue fluid homeostasis, absorption of dietary fats and trafficking of immune cells. Pannexin1 (Panx1) channels allow for the passage of ions and small metabolites between the cytosol and extracellular environment. Panx1 channels regulate the pathophysiological function of several tissues in a sex-dependent manner. Here, we studied the role of Panx1 in lymphatic function, and potential sex-dependent differences therein, in Prox1-CreERT2Panx1fl/fl and Panx1fl/fl control mice. Panx1 expression was higher in lymphatic endothelial cells (LECs) of male mice. Lymphatic vessel morphology was not affected in Prox1-CreERT2Panx1fl/fl male and female mice. Lymphatic drainage was decreased by 25% in male Prox1-CreERT2Panx1fl/fl mice, but was similar in females of both genotypes. Accordingly, only male Prox1-CreERT2Panx1fl/fl mice exhibited tail swelling, pointing to interstitial fluid accumulation in males upon Panx1 deletion in LECs. Moreover, serum triglyceride and free fatty acid levels raised less in Prox1-CreERT2Panx1fl/fl mice of both sexes in an oral lipid tolerance test. Finally, the percentage of migratory dendritic cells arriving in draining lymph nodes was increased in Prox1-CreERT2Panx1fl/fl female mice, but was comparable between male mice of both genotypes. Our results point to a LEC-specific role for Panx1 in the functions of the lymphatic system.
摘要：
毛细血管和收集血管的淋巴网络确保组织液稳态，饮食脂肪的吸收和免疫细胞的运输。Pannexin1（Panx1）通道允许离子和小代谢物在细胞质和细胞外环境之间通过。Panx1通道以性别依赖性方式调节几种组织的病理生理功能。这里,我们研究了Panx1在淋巴功能中的作用,以及其中潜在的性别依赖性差异，在Prox1-CreERT2Panx1fl/fl和Panx1fl/fl对照小鼠中。panx1在雄性小鼠淋巴内皮细胞（LECs）中表达较高。在Prox1-CreERT2Panx1fl/fl雄性和雌性小鼠中,淋巴管形态不受影响。雄性Prox1-CreERT2Panx1fl/fl小鼠的淋巴引流减少了25％，但在两种基因型的女性中相似。因此，只有雄性Prox1-CreERT2Panx1fl/fl小鼠出现尾部肿胀，指出LEC中Panx1缺失后男性的间质液积聚。此外，在口服脂质耐量试验中，两种性别的Prox1-CreERT2Panx1fl/fl小鼠的血清甘油三酸酯和游离脂肪酸水平升高较少。最后,在Prox1-CreERT2Panx1fl/fl雌性小鼠中，到达引流淋巴结的迁移树突状细胞的百分比增加，但在两种基因型的雄性小鼠之间具有可比性。我们的结果表明，Panx1在淋巴系统功能中具有LEC特异性作用。
