Abstract
The molecular mechanisms governing the formation of lymphatic vasculature are not yet well understood. Pannexins are transmembrane proteins that form channels which allow for diffusion of ions and small molecules (<1 kDa) between the extracellular space and the cytosol. The expression and function of pannexins in blood vessels have been studied in the last few decades. Meanwhile, no studies have been conducted to evaluate the role of pannexins during human lymphatic vessel formation. Here we show, using primary human dermal lymphatic endothelial cells (HDLECs), pharmacological tools (probenecid, Brilliant Blue FCF, mimetic peptides [10Panx]) and siRNA-mediated knockdown that Pannexin-1 is necessary for capillary tube formation on Matrigel and for VEGF-C-induced invasion. These results newly identify Pannexin-1 as a protein highly expressed in HDLECs and its requirement during in vitro lymphangiogenesis.
Highlights
Pannexin-1 (PANX1) is one of the three members of the Pannexin family with PANX2 and PANX3 discovered through homology to the invertebrate gap-junction forming proteins, innexins [1,2]
This study aims to investigate the expression of PANXs in human lymphatic endothelial cells and more the role of PANX1 during lymphangiogenesis
PANX1, -2 and -3 mRNA expression was examined by quantitative room temperature (RT)-PCR in human lymphatic endothelial cells
Summary
Pannexin-1 (PANX1) is one of the three members of the Pannexin family with PANX2 and PANX3 discovered through homology to the invertebrate gap-junction forming proteins, innexins [1,2]. Pannexins (PANXs) and Connexins (CXs) share similar protein structure while they lack amino acid sequence homology [3]. PANX1 is ubiquitously expressed in several organs and tissues [2,8,9,10,11,12] and is the best characterized isoform of the PANX family. PANX2 expression has been restricted to the central nervous system [13], but it is well described that PANX2 is ubiquitously distributed throughout the body [14]. PANX3 has been mainly described in cartilage, bone and skin [2,11,15,16,17,18,19,20,21] but accumulating evidences show PANX3 expression in other tissues such as skeletal muscle, heart, cochlea, and arteries [2,15,18,22,23]
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