Colonic Proteome Signature in Immunoproteasome-Deficient Stressed Mice and Its Relevance for Irritable Bowel Syndrome

Abstract

A role for immunoproteasome in the regulation of intestinal permeability has been previously suggested both in mice during water avoidance stress (WAS) and in patients with irritable bowel syndrome (IBS). Here, we provide evidence that the ubiquitin-proteasome system (UPS) contributes to the pathophysiology of IBS. Indeed, we report that colonic proteome is altered in WAS mice and that β2i subunit deficiency modifies the proteome response that is associated with a limitation of colonic hyperpermeability. Interestingly, we show specific alterations of proteins involved in UPS, mitochondrial and energy metabolism. We also report changes in the pattern of colonic ubiquitome in diarrhea-predominant IBS patients (IBS-D), and particularly a reduced expression of ubiquitinated proteins involved in the NF-κB inflammatory signaling pathway. All these data suggest that immunoproteasome targeting may represent a new therapeutic strategy for the treatment of IBS patients with increased intestinal permeability.

Stress-induced intestinal barrier dysfunction is exacerbated during diet-induced obesity

“…Finally, in the present study, due to the high fat diet, WAS procedure was performed in five months old mice. We cannot exclude that the response to WAS could be different compared to younger mice [16,22].…”

“…In the present study, we showed that HFD mice submitted to WAS model exhibited both increased intestinal permeability, compared to obese mice and to non-obese WAS mice, and increased plasma corticosterone levels. Previous data showed that both HFDinduced obesity [15] and WAS [16,22] are associated with increased intestinal permeability.…”

“…The water avoidance stress (WAS) model, commonly used to mimic IBS [22], was performed as previously described [16]. Briefly, mice were placed on a small platform in a tank of water (25°C) during one hour per day during ten consecutive days.…”

Comparative proteomic analysis of the brain and colon in three rat models of irritable bowel syndrome

“…The protein ubiquitination pathway and mitochondrial dysfunction were signaling pathways common to both the colon and the brain of the three IBS models. A recent study demonstrated reduced expression of colonic ubiquitinated proteins in IBS-D [22], confirming that the abnormal ubiquitination pathway plays a key role in the pathogenesis of IBS. By exploring the global possible protein-protein interactions (PPIs) (Fig.…”

In Vivo Quantitative Photoacoustic Diagnosis of Gastric and Intestinal Dysfunctions with a Broad pH-Responsive Sensor

“…Gastrointestinal dysfunctions such as gastroparesis, gastroesophageal reflux disease, irritable bowel syndrome, enteric dysmotility, and Crohn’s disease affect people’s life quality, nutrition, and work efficiency, leading to considerable health care costs. − In particular, peptic ulcers and ulcerative colitis are the most prevalent diseases, accounting for ∼4% of the world’s population . In the United States, work losses from peptic ulcers and annual medical costs related with in-patient and out-patient care are estimated to be $5.65 billion every year .…”