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金属肽酶 ADAM 样解整合素 1(ADAMDEC1)在结肠黏膜下 PDGFRα 细胞中是炎症性肠病的新标志物。

Metalloendopeptidase ADAM-like Decysin 1 (ADAMDEC1) in Colonic Subepithelial PDGFRα Cells Is a New Marker for Inflammatory Bowel Disease.

机构信息

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

Department of Physiology, Wonkwang Digestive Disease Research Institute and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan 54538, Korea.

出版信息

Int J Mol Sci. 2022 Apr 30;23(9):5007. doi: 10.3390/ijms23095007.

Abstract

Metalloendopeptidase ADAM-Like Decysin 1 (ADAMDEC1) is an anti-inflammatory peptidase that is almost exclusively expressed in the gastrointestinal (GI) tract. We have recently found abundant and selective expression of Adamdec1 in colonic mucosal PDGFRα cells. However, the cellular origin for this gene expression is controversial as it is also known to be expressed in intestinal macrophages. We found that Adamdec1 mRNAs were selectively expressed in colonic mucosal subepithelial PDGFRα cells. ADAMDEC1 protein was mainly released from PDGFRα cells and accumulated in the mucosal layer lamina propria space near the epithelial basement membrane. PDGFRα cells significantly overexpressed Adamdec1 mRNAs and protein in DSS-induced colitis mice. Adamdec1 was predominantly expressed in CD45 PDGFRα cells in DSS-induced colitis mice, with only minimal expression in CD45 CD64 macrophages. Additionally, overexpression of both ADAMDEC1 mRNA and protein was consistently observed in PDGFRα cells, but not in CD64 macrophages found in human colonic mucosal tissue affected by Crohn's disease. In summary, PDGFRα cells selectively express ADAMDEC1, which is localized to the colon mucosa layer. ADAMDEC1 expression significantly increases in DSS-induced colitis affected mice and Crohn's disease affected human tissue, suggesting that this gene can serve as a diagnostic and/or therapeutic target for intestinal inflammation and Crohn's disease.

摘要

金属肽酶 ADAM 样解聚素 1(ADAMDEC1)是一种抗炎肽酶,几乎仅在胃肠道(GI)中表达。我们最近发现 Adamdec1 在结肠黏膜 PDGFRα 细胞中大量且选择性地表达。然而,由于它也已知在肠道巨噬细胞中表达,因此对于这种基因表达的细胞来源存在争议。我们发现 Adamdec1 mRNAs 选择性地表达在结肠黏膜上皮下 PDGFRα 细胞中。ADAMDEC1 蛋白主要从 PDGFRα 细胞释放并积聚在靠近上皮基底膜的黏膜层固有层空间中。PDGFRα 细胞在 DSS 诱导的结肠炎小鼠中显着过表达 Adamdec1 mRNAs 和蛋白。在 DSS 诱导的结肠炎小鼠中,Adamdec1 主要在 CD45 PDGFRα 细胞中表达,在 CD45 CD64 巨噬细胞中表达很少。此外,在 PDGFRα 细胞中一致观察到 ADAMDEC1 mRNA 和蛋白的过表达,但在受克罗恩病影响的人类结肠黏膜组织中的 CD64 巨噬细胞中观察到的则很少。总之,PDGFRα 细胞选择性地表达 ADAMDEC1,其定位于结肠黏膜层。ADAMDEC1 在 DSS 诱导的结肠炎小鼠和受克罗恩病影响的人类组织中的表达显着增加,表明该基因可以作为肠道炎症和克罗恩病的诊断和/或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7571/9103908/bda2bd97ae08/ijms-23-05007-g001.jpg

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