Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease

Hosomi, Shuhei; Kaser, Arthur; Blumberg, Richard S.

doi:10.1097/mog.0000000000000144

Cited by 69 publications

(63 citation statements)

References 66 publications

(83 reference statements)

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“…The link between the IRE1α pathway of the UPR and NOD1/2 is of particular interest for CD, since this inflammatory pathology has been linked to ER stress-mediated dysfunction of Paneth cells (reviewed in [78, 79]). Interestingly, two proteins affected by CD-associated risk alleles, ATG16L1, required for autophagy, and XBP1, a regulator of the unfolded protein response, alleviate ER stress and reduce activation of the IRE1α pathway.…”

Section: Nod1/2 Sensing Of Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

NOD1 and NOD2: Beyond Peptidoglycan Sensing

Keestra-Gounder

Tsolis²

2017

Trends in Immunology

108

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NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that NODs can also recognize a broader array of danger signals. Indeed, recent work has expanded the roles of NOD1 and NOD2 to encompass not only sensing of infections with viruses and parasites but also perceiving perturbations of cellular processes such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis. This review will comment on recent progress and point out emerging questions in these areas.

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Section: Nod1/2 Sensing Of Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

NOD1 and NOD2: Beyond Peptidoglycan Sensing

Keestra-Gounder

Tsolis²

2017

Trends in Immunology

108

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“…This process can be promoted by autophagy (45–47). Evidence has shown that impaired autophagy disturbs the function of intestinal epithelial cells and influences the innate and adaptive immune responses, ROS production, and endoplasmic reticulum (ER) stress, leading to abnormal inflammatory reaction, and ultimately promoting the occurrence and development of IBD (7, 48–50). …”

Section: The Roles Of Autophagy In Ibdmentioning

confidence: 99%

Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

Peng

Shao

et al. 2017

Front. Immunol.

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Intestinal mucosal barrier, mainly composed of the intestinal mucus layer and the epithelium, plays a critical role in nutrient absorption as well as protection from pathogenic microorganisms. It is widely acknowledged that the damage of intestinal mucosal barrier or the disturbance of microorganism balance in the intestinal tract contributes greatly to the pathogenesis and progression of inflammatory bowel disease (IBD), which mainly includes Crohn’s disease and ulcerative colitis. Autophagy is an evolutionarily conserved catabolic process that involves degradation of protein aggregates and damaged organelles for recycling. The roles of autophagy in the pathogenesis and progression of IBD have been increasingly studied. This present review mainly describes the roles of autophagy of Paneth cells, macrophages, and goblet cells in IBD, and finally, several potential therapeutic strategies for IBD taking advantage of autophagy.

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“…Recent reports suggested that the macro-autophagy (hereafter autophagy) pathway, an evolutionarily conserved cellular protein degradation mechanism, contributes to ER stress [12, 13]. Autophagy is a catabolic process for autophagosome-lysosomal degradation of bulk cytoplasmic content of proteins.…”

Section: Introductionmentioning

confidence: 99%

Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

Ghosh

Mau

O’Brien

et al. 2016

Aging

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Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort. Elevated expressions of ER-stress marker CHOP and autophagy substrate SQSTM1/p62 are observed in old SVFs compared to young, when treated with either vehicle or with thapsigargin (Tg), an ER stress inducer. Treatment with bafilomycin A1 (Baf), a vacuolar-type H (+)-ATPase, or Tg elevated expressions of CHOP, and SQSTM1/p62 and LC-3-II, in 3T3-L1-preadipocytes. We also demonstrate impaired autophagy activity in old SVFs by analyzing increased accumulation of autophagy substrates LC3-II and p62. Compromised autophagy activity in old SVFs is correlated with enhanced release of pro-inflammatory cytokines IL-6 and MCP-1. Finally, SVFs from calorie restricted old mice (CR-O) have shown enhanced autophagy activity compared to ad libitum fed old mice (AL-O). Our results support the notion that diminished autophagy activity with aging contributes to increased adipose tissue ER stress and inflammation.

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Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease

Cited by 69 publications

References 66 publications

NOD1 and NOD2: Beyond Peptidoglycan Sensing

NOD1 and NOD2: Beyond Peptidoglycan Sensing

Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

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