Meens Merlijn J, Kutkut Issa, Rochemont Viviane, Dubrot Juan, Kaladji Fouad R, Sabine Amélie, Lyons Oliver, Hendrikx Stefanie, Bernier-Latmani Jeremiah, Kiefer Friedemann, Smith Alberto, Hugues Stéphanie, Petrova Tatiana V, Kwak Brenda R
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland.
PLoS One. 2017 Jul 21;12(7):e0181476. doi: 10.1371/journal.pone.0181476. eCollection 2017.
Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency. Cx47 is dispensable for long-chain fatty acid absorption from the gut but rather promotes serum lipid handling as prolonged elevated triglyceride levels were observed in Cx47-deficient mice after oral lipid tolerance tests. When crossed with Apolipoprotein E-deficient (Apoe-/-) mice, LDL-cholesterol was decreased in young Cx47-/-Apoe-/- adults as compared to Apoe-/- mice, which was inverted later in life. Finally, advanced atherosclerotic plaques in thoracic-abdominal aortas of 15 months-old mice tended to be larger in Cx47-/-Apoe-/- mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of Apoe-/- mice. In conclusion, Cx47 is expressed in lymphatic endothelium and seems modestly implicated in multiple aspects of lymphatic pathophysiology.
缝隙连接蛋白连接蛋白47（Cx47）的突变与淋巴水肿有关。然而，Cx47在淋巴病理生理学中的作用尚不清楚。我们通过全组织免疫染色和定量聚合酶链反应证明Cx47在淋巴管内皮细胞中表达。为了确定Cx47是否在淋巴管功能中起作用，我们分析了Cx47基因敲除小鼠。Cx47缺乏并不影响淋巴管的收缩性（收缩幅度或频率）或淋巴管形态（血管直径或瓣膜数量）。Cx47缺乏也不影响间质液通过淋巴管的引流或树突状细胞的迁移。Cx47对于肠道中长链脂肪酸的吸收不是必需的，但在口服脂质耐量试验后，Cx47基因敲除小鼠中观察到甘油三酯水平长期升高，这表明Cx47反而促进血清脂质的处理。当与载脂蛋白E缺乏（Apoe-/-）小鼠杂交时，与Apoe-/-小鼠相比，年轻的Cx47-/-Apoe-/-成年小鼠的低密度脂蛋白胆固醇降低，而在生命后期这种情况则相反。最后，15个月龄小鼠胸主动脉中的晚期动脉粥样硬化斑块在Cx47-/-Apoe-/-小鼠中往往更大。这些斑块中的巨噬细胞比Apoe-/-小鼠的斑块少，但T淋巴细胞、胶原蛋白和脂质的含量相似。总之，Cx47在淋巴管内皮中表达，似乎在淋巴病理生理学的多个方面有适度的影响。
