Hyaluronan Synthase 3 Null Mice Exhibit Decreased Intestinal Inflammation and Tissue Damage in the DSS-Induced Colitis Model.
Hyaluronan Synthase 3 Null Mice Exhibit Decreased Intestinal Inflammation and Tissue Damage in the DSS-Induced Colitis Model.
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DOI：
10.1155/2015/745237
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发表时间：
2015
影响因子：
--
通讯作者：
de la Motte C
中科院分区：
文献类型：
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作者：
Kessler SP;Obery DR;de la Motte C
透明质酸（HA）的过度产生是多种炎性疾病的标志，包括炎性肠病（IBD）。Hybryonan可以作为白细胞募集分子，在最常见的肠道炎症小鼠模型，化学诱导的葡聚糖硫酸钠（DSS）实验性结肠炎模型中，我们先前确定HA的结肠分布变化发生在炎症之前。因此，我们假设，在病理挑战，HA促进炎症。在这项研究中，我们测试了DSS-结肠炎模型中透明质酸合酶基因（HAS 1，HAS 3，或HAS 1和HAS 3）缺失小鼠的炎症进展。我们的数据表明，HAS 1/HAS 3双和HAS 3无效小鼠都受到保护，从结肠炎，与野生型和HAS 1无效小鼠相比，如通过测量体重减轻，疾病活动，血清IL-6水平，组织学评分和免疫组织化学。最值得注意的是粘膜下微血管系统，透明质酸沉积，白细胞浸润的野生型和HAS 1基因敲除小鼠的炎症结肠组织中的显着增加。我们的数据表明，HAS 3在驱动肠道炎症中起着至关重要的作用。在微循环中开发HAS 3表达或功能的临时靶向治疗干预可能成为缓解IBD发作患者结肠炎的理想策略。
Hyaluronan (HA) overproduction is a hallmark of multiple inflammatory diseases, including inflammatory bowel disease (IBD). Hyaluronan can act as a leukocyte recruitment molecule and in the most common mouse model of intestinal inflammation, the chemically induced dextran sodium sulfate (DSS) experimental colitis model, we previously determined that changes in colon distribution of HA occur before inflammation. Therefore, we hypothesized that, during a pathologic challenge, HA promotes inflammation. In this study, we tested the progression of inflammation in mice null for the hyaluronan synthase genes (HAS1, HAS3, or both HAS1 and HAS3) in the DSS-colitis model. Our data demonstrate that both the HAS1/HAS3 double and the HAS3 null mice are protected from colitis, compared to wild-type and HAS1 null mice, as determined by measurement of weight loss, disease activity, serum IL-6 levels, histologic scoring, and immunohistochemistry. Most notable is the dramatic increase in submucosal microvasculature, hyaluronan deposition, and leukocyte infiltration in the inflamed colon tissue of wild-type and HAS1 null mice. Our data suggest, HAS3 plays a crucial role in driving gut inflammation. Developing a temporary targeted therapeutic intervention of HAS3 expression or function in the microcirculation may emerge as a desirable strategy toward tempering colitis in patients undergoing flares of IBD.