Accumulation of versican and lack of versikine ameliorate acute colitis
Accumulation of versican and lack of versikine ameliorate acute colitis
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DOI：
10.1016/j.matbio.2022.02.004
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发表时间：
2022-02-24
期刊：
影响因子：
6.9
通讯作者：
Watanabe, Hideto
中科院分区：
文献类型：
--
作者：
Islam, Shamima;Jahan, Nushrat;Watanabe, Hideto
Versican是一种大型硫酸软骨素/硫酸皮肤聚糖蛋白多糖，在临时基质的形成中起关键作用。在这里，我们在敲入小鼠（R/R）中产生葡聚糖硫酸钠诱导的结肠炎，表达ADAMTS-resistant versican，并研究versican在炎性结肠粘膜中的积累及其转化的影响。组织学上，R/R结肠显示组织破坏水平降低，肌成纤维细胞和巨噬细胞数量增加。炎性细胞表征显示，与野生型相比，R/R结肠中F4/80+巨噬细胞增加，M1和M2群体之间没有明显的变化。肠间质在R/R中显示出更多的肌成纤维细胞，表明组织再生水平增加。从炎性结肠中获得的巨噬细胞与间质成纤维细胞共培养表明，野生型巨噬细胞抑制R/R成纤维细胞向肌成纤维细胞分化，而野生型无抑制作用。这种抑制作用是由于缬草碱水平的增加，缬草碱是由ADAMTS蛋白酶裂解的缬草碱片段。综上所述，我们的研究结果表明，毒藤碱是抑制炎症组织修复的直接调节剂。(C) 2022作者(s)。Elsevier B.V.出版
Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan that plays a key role in the formation of the provisional matrix. Here, we generated dextran sulfate sodium-induced colitis in knockin-mice, R/R, expressing ADAMTS-resistant versican, and investigated the impact of accumulating versican and its turnover in the inflammatory colon mucosa. Histologically, R/R colon showed decreased levels of tissue destruction and an increased number of myofibroblasts and macrophages. Characterization of inflammatory cells revealed an increase in F4/80+ macrophages in R/R colon, compared with wildtype, without a clear shift between M1 and M2 populations. Intestinal stroma exhibited a higher number of myofibroblasts in R/R, suggesting increased levels of tissue regeneration. Coculture of macrophages and stromal fibroblasts obtained from inflammatory colon showed that wild-type macrophages inhibited myofibroblastic differentiation of R/R fibroblasts but not wild-type. This inhibitory effect was due to an increased level of versikine, a cleaved fragment of versican by ADAMTS proteinases. Taken together, our results demonstrate versikine as the direct regulator that inhibits repair of inflamed tissue. (C) 2022 The Author(s). Published by Elsevier B.V.