Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease

Abstract

Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory bowel disease (IBD). IBD is a complicated inflammatory colitis disorder; Crohn’s disease and ulcerative colitis are the principal types. Genetic studies have shown the clinical relevance of several autophagy-related genes (ATGs) in the pathogenesis of IBD. Additionally, recent studies using conditional knockout mice have led to a comprehensive understanding of ATGs that affect intestinal inflammation, Paneth cell abnormality and enteric pathogenic infection during colitis. In this review, we discuss the various ATGs involved in macroautophagy and selective autophagy, including ATG16L1, IRGM, LRRK2, ATG7, p62, optineurin and TFEB in the maintenance of intestinal homeostasis. Although advances have been made regarding the involvement of ATGs in maintaining intestinal homeostasis, determining the precise contribution of autophagy has remained elusive. Recent efforts based on direct targeting of ATGs and autophagy will further facilitate the development of new therapeutic opportunities for IBD.

New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

“…Autophagy was initially characterized as a nonspecific process induced under starvation conditions to recycle building blocks to compensate for the lack of nutrients, and thus was so-called nonselective bulk autophagy. Later, it has been evidenced that autophagy can be induced in non-starved cells to degrade specific substrates, such as aggregated proteins, damaged mitochondria or invading pathogens, which is known as selective autophagy [4]. Autophagy plays a key role in maintaining intestinal homeostasis, in regulating the interaction between gut microbiota and innate and adaptive immunity, and in host defense against intestinal pathogens [3].…”

Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis

“…For example, among the genetic factors associated with the UC etiology, variants in the autophagy-related genes have been identified. Recent studies have shown that autophagy played a key role in maintaining intestinal homeostasis and regulating the interaction between gut microbiota and innate and adaptive immunity [ 16 , 17 ]. Therefore, the research progress of UC molecular mechanism based on microarray technology can provide potential targets for the diagnosis and treatment of UC.…”

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn’s disease via signaling involving distinct classes of phosphatidylinositol 3-kinases

“…This type of autophagy can be triggered by different stimuli, such as starvation, inflammation, oxidative stress, hypoxia, and toxic molecules. Studies have shown that dysregulation of autophagy is inextricably linked to the occurrence and development of CD[ 6 , 7 ]. Thus, in the present study, we used the Morris method to establish a rat model of CD and observed the effects of TNBS on colonic autophagy in rats.…”

“…Autophagy maintains intracellular homeostasis and promotes cell survival by decomposing related intracellular substrates[ 5 ]. Increasing evidence suggests that dysregulation of autophagy is inextricably linked to the onset of CD[ 6 , 11 ]. For example, autophagic dysfunction can reduce the restriction of intracellular replication of adherent-invasive E. coli (AIEC) and increase the secretion of proinflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the intestine[ 12 , 13 ].…”