Department of Basic Medical Sciences, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy.
Histochem Cell Biol. 2012 May;137(5):669-77. doi: 10.1007/s00418-012-0910-y. Epub 2012 Jan 12.
Neuropilin-1 (NRP1) is a transmembrane co-receptor for members of the vascular endothelial growth factor family. Recent studies revealed an important role of NRP1 in angiogenesis and progression of many diseases. The role of NRP1 in the development of Sjögren's syndrome (SS), one of the most common rheumatic diseases, has not yet been investigated. Molecular studies and protein expression techniques were performed to elucidate the gene and protein expression profile of NRP1 in human salivary gland epithelial cells (SGEC) from primary SS. We used human microarrays and transient transfection with a mutant form of the negative inhibitory κBα proteins (IκBαDN) to investigate whether selective inhibition of nuclear Factor-κB (NF-κB) improves NRP1-mediated pro-angiogenic factors release from SS SGEC. The selective NRP1 function inhibition with an antibody to human NRP1, was employed to evaluate the therapeutic potential of targeting NRP1. We demonstrate that NRP1 is expressed in SGEC of both human healthy biopsies and in SS samples, and increased NRP1 expression in SS SGEC is significantly associated with pro-angiogenic factors release. Neutralizing anti-NRP1 antibody decreased pro-angiogenic factor production from SS SGEC and blocking NF-κB activation could be a way to inhibit NRP1-mediated angiogenesis in Sjögren's syndrome.
神经纤毛蛋白-1（NRP1）是血管内皮生长因子家族成员的跨膜共受体。最近的研究揭示了 NRP1 在许多疾病的血管生成和进展中的重要作用。NRP1 在干燥综合征（SS），最常见的风湿性疾病之一的发展中的作用尚未被研究。进行了分子研究和蛋白质表达技术，以阐明原发性 SS 患者唾液腺上皮细胞（SGEC）中 NRP1 的基因和蛋白质表达谱。我们使用人类微阵列和瞬时转染负抑制κBα蛋白（IκBαDN）的突变形式，以研究选择性抑制核因子-κB（NF-κB）是否改善 SS SGEC 中 NRP1 介导的促血管生成因子释放。用抗人 NRP1 的抗体对 NRP1 进行选择性功能抑制，以评估靶向 NRP1 的治疗潜力。我们证明 NRP1 在人健康活检和 SS 样本的 SGEC 中表达，并在 SS SGEC 中表达增加的 NRP1 与促血管生成因子的释放显著相关。中和抗 NRP1 抗体可减少 SS SGEC 中促血管生成因子的产生，并且阻断 NF-κB 激活可能是抑制干燥综合征中 NRP1 介导的血管生成的一种方法。
