Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair

Author:

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

Abstract

Abstract Background 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. Results 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. Conclusion Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair.

Funder

National Natural Science Foundation of China

Yunnan young academic and technical leaders reserve talent project

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Molecular Biology,Biochemistry

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