Department of Cardiovascular Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan.
Mol Biol Rep. 2023 Oct;50(10):7981-7993. doi: 10.1007/s11033-023-08620-0. Epub 2023 Aug 4.
Accumulating evidence suggests that prostaglandin E, an arachidonic acid (AA) metabolite, enhances lymphangiogenesis in response to inflammation. However, thromboxane A (TXA), another AA metabolite, is not well known. Thus, this study aimed to determine the role of thromboxane prostanoid (TP) signaling in lymphangiogenesis in secondary lymphedema.
Lymphedema was induced by the ablation of lymphatic vessels in mouse tails. Compared with wild-type mice, tail lymphedema in Tp-deficient mice was enhanced, which was associated with suppressed lymphangiogenesis as indicated by decreased lymphatic vessel area and pro-lymphangiogenesis-stimulating factors. Numerous macrophages were found in the tail tissues of Tp-deficient mice. Furthermore, the deletion of TP in macrophages increased tail edema and decreased lymphangiogenesis and pro-lymphangiogenic cytokines, which was accompanied by increased numbers of macrophages and gene expression related to a pro-inflammatory macrophage phenotype in tail tissues. In vivo microscopic studies revealed fluorescent dye leakage in the lymphatic vessels in the wounded tissues.
The results suggest that TP signaling in macrophages promotes lymphangiogenesis and prevents tail lymphedema. TP signaling may be a therapeutic target for improving lymphedema-related symptoms by enhancing lymphangiogenesis.
越来越多的证据表明，前列腺素 E（一种花生四烯酸（AA）代谢物）可增强炎症反应中的淋巴管生成。然而，血栓烷 A（TXA）作为另一种 AA 代谢物，其作用尚未得到充分了解。因此，本研究旨在确定血栓烷前列腺素（TP）信号在继发性淋巴水肿中的淋巴管生成中的作用。
通过消融小鼠尾巴中的淋巴管来诱导淋巴水肿。与野生型小鼠相比，Tp 缺陷型小鼠的尾巴淋巴水肿增强，这与淋巴管面积减少和促淋巴管生成刺激因子减少有关，表明淋巴管生成受到抑制。Tp 缺陷型小鼠的尾巴组织中存在大量巨噬细胞。此外，巨噬细胞中 TP 的缺失增加了尾巴水肿，减少了淋巴管生成和促淋巴管生成细胞因子，这伴随着尾巴组织中巨噬细胞数量的增加和与促炎型巨噬细胞表型相关的基因表达。体内显微镜研究显示，受伤组织中的淋巴管有荧光染料渗漏。
研究结果表明，巨噬细胞中的 TP 信号促进淋巴管生成并预防尾巴淋巴水肿。TP 信号可能是通过增强淋巴管生成来改善淋巴水肿相关症状的治疗靶点。
