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Cell death of intestinal epithelial cells in intestinal diseases

Saravanan Subramanian^1,2, Hua Geng^1,2, Xiao-Di Tan^1,2,3,*

¹Center for Intestinal and Liver Inflammation Research, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois 60611, USA；²Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA；³Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

Abstract

Gut injury continues to be the devastating and unpredictable critical illness associated with increased cell death of intestinal epithelial cells (IECs). The IECs, immune system and microbiome are the interrelated entities to maintain normal intestinal homeostasis and barrier integrity. In response to microbial invasion, IEC cell death occurs to maintain intestinal epithelium function and retain the continuous renewal and tissue homeostasis. But the imbalance of IEC cell death results in increased intestinal permeability and barrier dysfunction that leads to several acute and chronic intestinal diseases, such as intestinal ischemia/reperfusion (I/R), sepsis, inflammatory bowel diseases (IBD), necrotizing enterocolitis (NEC), etc. During the pathophysiological state, the excessive IEC apoptotic cell death leads to a chronic inflammatory condition, later switches to necroptotic cell death mechanism that induces more pathological features than apoptosis and may also induce other lytic cell death mechanisms like pyroptosis and ferroptosis to increase the pathogenesis of the intestinal diseases. But still, there remains gaps in the fundamental knowledge about the IEC cell death mechanisms in chronic intestinal diseases. Together, a deep understanding of the specific cell death mechanisms underlying chronic intestinal diseases, including sepsis, IBD, NEC, and intestinal I/R, is desperately needed to develop emerging novel promising therapeutic strategies. This review aims to show how the acute and critical illness in the gut are driven by IEC cell death mechanism, such as apoptosis, necrosis, necroptosis, pyroptosis, and ferroptosis. 

Key words: intestinal epithelial cells; apoptosis; necroptosis; pyroptosis; ferroptosis; intestinal diseases

Received: 2019-10-25　　Accepted: 2020-03-05

Corresponding author: 谭小弟　　E-mail: xtan@northwestern.edu

DOI: 10.13294/j.aps.2020.0039

Citing This Article：

Saravanan Subramanian, Hua Geng, Xiao-Di Tan. Cell death of intestinal epithelial cells in intestinal diseases. Acta Physiol Sin 2020; 72 (3): 308-324