Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.
Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.
复制标题
胱硫醚γ裂解酶 (Cth) 通过 ERK1/2 诱导巨噬细胞胞吞作用，从而调节肠道屏障修复
DOI：
10.1186/s12964-022-01030-y
复制
发表时间：
2023-01-23
影响因子：
8.4
通讯作者：
Sun, Da-Li
中科院分区：
文献类型：
--
作者：
Zhao, Xiao-Hu;Yang, Ting;Zheng, Meng-Yao;Zhao, Peinan;An, Li-Ya;Qi, Yu-Xing;Yi, Ke-Qian;Zhang, Peng-Cheng;Sun, Da-Li
关键词：
肠缺血再灌注损伤（I/R）诱导的炎症反应与危重患者的感染并发症和死亡率密切相关，及时有效地清除凋亡细胞是减轻炎症反应的重要环节。研究表明，吞噬细胞的吞噬作用起着重要作用。近年来，利用小肠类器官模型的研究表明，巨噬细胞吞噬作用可促进肠上皮细胞的修复能力。然而，没有研究报道在I/R的动物模型的修复中的巨噬细胞。我们采用在体巨噬细胞吞噬试验发现巨噬细胞吞噬在I/R后肠屏障功能的修复和维持中起着不可或缺的作用。此外，Cth-ERK 1/2依赖性是诱导巨噬细胞吞噬的特异性分子机制。我们发现，Cth驱动巨噬细胞吞噬细胞在体内和体外。过表达/沉默Cth分别促进/抑制ERK 1/2通路，这反过来又影响了细胞增殖和介导的肠屏障恢复。此外，我们发现Cth和巨噬细胞吞噬功能与临床患者肠功能的恢复呈正相关。Cth可以激活ERK 1/2信号通路，诱导巨噬细胞吞噬，从而促进肠屏障修复。视频摘要在线版本包含补充材料，可通过10. 1186/s12964-022-01030-y获取。
The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract The online version contains supplementary material available at 10.1186/s12964-022-01030-y.
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影响因子：
2.4
作者：
Nadatani Y;Watanabe T;Shimada S;Otani K;Tanigawa T;Fujiwara Y
通讯作者：
Fujiwara Y
影响因子：
8
作者：
Cai, Wei;Dai, Xuejiao;Chen, Jun
通讯作者：
Chen, Jun
影响因子：
9.3
作者：
Lee, Ha-Rim;Lee, Jeewoo;Kim, Hyun-Jung
通讯作者：
Kim, Hyun-Jung
影响因子：
3.7
作者：
Lahey KA;Ronaghan NJ;Shang J;Dion SP;Désilets A;Leduc R;MacNaughton WK
通讯作者：
MacNaughton WK
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD