MKL1 expressed in macrophages contributes to the development of murine colitis.
MKL1 expressed in macrophages contributes to the development of murine colitis.
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DOI：
10.1038/s41598-017-13629-0
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发表时间：
2017-10-20
影响因子：
4.6
通讯作者：
Kimura A
中科院分区：
文献类型：
--
作者：
An J;Nagaishi T;Watabe T;Naruse TK;Watanabe M;Kimura A
缺乏巨核细胞白血病1（Mkl 1）基因的小鼠经历了不太严重的葡聚糖硫酸钠（DSS）诱导的结肠炎，这意味着Mkl 1在炎症性肠病（IBD）中起着病理作用。然而，Mkl 1对结肠炎发展的贡献仍有待阐明。DSS处理小鼠结肠固有层巨噬细胞（LPMac）中Mkl 1的表达高于对照小鼠。因此，我们建立了一个转基因小鼠系，过表达人MKL 1（MKL 1-Tg），特别是在单核细胞/巨噬细胞系的细胞，以调查的潜在作用，巨噬细胞MKL 1在结肠炎的发病机制。MKL 1-Tg小鼠表现出自发性结肠缩短和直肠脱垂。流式细胞术和定量RT-PCR分析显示，与同窝对照小鼠相比，MKL 1-Tg小鼠中的LPMac数量减少，并且具有指示抗炎特性受损的炎性表型改变，而MKL 1-Tg小鼠的骨髓源性巨噬细胞偏向M1极化。此外，MKL 1-Tg小鼠对DSS诱导的结肠炎的易感性高于其同窝对照小鼠。这些观察结果表明，MKL 1通过调节巨噬细胞的功能对结肠炎的发展至关重要，这表明它可能是预防IBD的潜在治疗靶点。
Mice deficient in the megakaryoblastic leukaemia 1 (Mkl1) gene experience less severe dextran sulphate sodium (DSS)-induced colitis, implying that Mkl1 plays a pathological role in inflammatory bowel disease (IBD). However, the contribution of Mkl1 to the development of colitis remains to be elucidated. The expression of Mkl1 is higher in the colonic lamina propria macrophages (LPMac) of DSS-treated mice than in those of control mice. Therefore, we established a transgenic mouse line that overexpresses human MKL1 (MKL1-Tg) specifically in cells of the monocyte/macrophage lineage, in order to investigate the potential role of macrophage MKL1 in the pathogenesis of colitis. MKL1-Tg mice displayed spontaneous colon shortening and rectal prolapse. Flow cytometric and quantitative RT-PCR analyses revealed that, in MKL1-Tg mice compared to littermate controls, the population of LPMac was decreased and had an altered inflammatory phenotype indicative of impaired anti-inflammatory properties, whereas bone marrow-derived macrophages from MKL1-Tg mice skewed towards M1 polarisation. In addition, MKL1-Tg mice had higher susceptibility to DSS-induced colitis than their littermate controls. These observations indicated that MKL1 crucially contributes to the development of colitis via the regulation of the function of macrophages, suggesting that it may be a potential therapeutic target for the prevention of IBD.
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DOI：
10.1038/nrm2890
发表时间：
2010-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Rani, Reena;Smulian, Alan G.;Greaves, David R.;Hogan, Simon P.;Herbert, De'Broski R.
通讯作者：
Herbert, De'Broski R.
DOI：
10.1084/jem.20100052
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lochner M;Ohnmacht C;Presley L;Bruhns P;Si-Tahar M;Sawa S;Eberl G
通讯作者：
Eberl G
影响因子：
--
作者：
Stevceva L;Pavli P;Husband AJ;Doe WF
通讯作者：
Doe WF
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto