Role of Autophagy Inducers and Inhibitors in Intestinal Barrier Injury Induced by Intestinal Ischemia–Reperfusion (I/R)

Abstract

Objectives. Intestinal epithelial barrier function is an important mechanical barrier to maintain intestinal homeostasis and resist the invasion of intestinal pathogens and microorganisms. However, intestinal epithelial barrier function is vulnerable to damage under intestinal ischemia–reperfusion (I/R) injury. Under a category of pathophysiological conditions, including I/R, autophagy plays a crucial role. This study is aimed at discussing the role of autophagy inhibitors and activators in intestinal epithelial barrier function after intestinal I/R by changing autophagy levels. Methods. Mice with intestinal IR underwent 45 minutes of surgery for superior mesenteric artery occlusion. The autophagy inhibitor 3-MA and the autophagy inducer rapamycin (RAP) were used to change the level of autophagy, and then, the expressions of tight junction proteins and intestinal barrier function were detected. Results. The results showed that the autophagy inhibitor 3-MA aggravated intestinal epithelial barrier dysfunction, while the autophagy inducer RAP attenuated intestinal epithelial barrier dysfunction. In addition, promoting autophagy may promote occludin expression by inhibiting claudin-2 expression. Conclusion. Upregulation of autophagy levels by autophagy inducers can enhance intestinal epithelial barrier function after intestinal I/R.

Mitochondrial Antiviral Pathways Control Anti-Hiv Responses and Ischemic Stroke Outcomes via the Rig-1 Signaling and Innate Immunity Mechanisms

“…7 ). Although some literature reports have linked ocln levels with both autophagy activation 93 – 95 and apoptosis 96 – 100 , the results are controversial, and this relationship was never studied in microvasculature. In contrast to our findings, a reduction in susceptibility to the induction of apoptosis in keratinocytes after ocln downregulation has been previously reported 96 .…”

Targeting cell death pathways in intestinal ischemia-reperfusion injury: a comprehensive review

“…Cells may perform autophagy to eliminate dysfunctional or anomalous organelles and proteins, thus obtaining energy and nutrients through the degradation of these cellular components to ensure survival. Upon reperfusion of blood flow into the ischemic intestine, an inflammatory response and cellular stress might occur, which might trigger autophagy as a cellular stress response mechanism to regulate the intracellular environment and facilitate cellular adaptation [ 95 , 96 ]. While examining intestinal I/R injury, autophagy flux was found to be impaired throughout the intestinal I/R procedure [ 97 ].…”

Advancements in the study of acute lung injury resulting from intestinal ischemia/reperfusion

“…Its involvement in physiological and pathological processes makes its role in various diseases intricate and contradictory. In the context of II/R, an inflammation-related illness, the relationship between autophagy and disease progression is closely intertwined ( 84 ). Researchers have proposed differing perspectives on the role of autophagy in this context.…”