Differential Transcriptomic Profiles Following Stimulation with Lipopolysaccharide in Intestinal Organoids from Dogs with Inflammatory Bowel Disease and Intestinal Mast Cell Tumor

Abstract

Lipopolysaccharide (LPS) is associated with chronic intestinal inflammation and promotes intestinal cancer progression in the gut. While the interplay between LPS and intestinal immune cells has been well-characterized, little is known about LPS and the intestinal epithelium interactions. In this study, we explored the differential effects of LPS on proliferation and the transcriptome in 3D enteroids/colonoids obtained from dogs with naturally occurring gastrointestinal (GI) diseases including inflammatory bowel disease (IBD) and intestinal mast cell tumor. The study objective was to analyze the LPS-induced modulation of signaling pathways involving the intestinal epithelia and contributing to colorectal cancer development in the context of an inflammatory (IBD) or a tumor microenvironment. While LPS incubation resulted in a pro-cancer gene expression pattern and stimulated proliferation of IBD enteroids and colonoids, downregulation of several cancer-associated genes such as Gpatch4, SLC7A1, ATP13A2, and TEX45 was also observed in tumor enteroids. Genes participating in porphyrin metabolism (CP), nucleocytoplasmic transport (EEF1A1), arachidonic acid, and glutathione metabolism (GPX1) exhibited a similar pattern of altered expression between IBD enteroids and IBD colonoids following LPS stimulation. In contrast, genes involved in anion transport, transcription and translation, apoptotic processes, and regulation of adaptive immune responses showed the opposite expression patterns between IBD enteroids and colonoids following LPS treatment. In brief, the crosstalk between LPS/TLR4 signal transduction pathway and several metabolic pathways such as primary bile acid biosynthesis and secretion, peroxisome, renin–angiotensin system, glutathione metabolism, and arachidonic acid pathways may be important in driving chronic intestinal inflammation and intestinal carcinogenesis.

A Review on Annona muricata and Its Anticancer Activity

“…While by serving as an immunomodulatory switch, members of the glycoprotein family, such as MUC1, can play either a pro- or anti-inflammatory role in various infection-induced malignancies [ 5 , 176 ], MUC4 plays an important role in the etiology of many different types of cancer, including pancreatic cancer (PC), ovarian cancers, and head and neck cancers (HNC) [ 114 , 152 ]. MUC4 suppresses apoptosis and induces resistance to several chemotherapeutic agents by modulating STAT and the PI-3K, Ras/RAF/extracellular signal-regulated kinase (ERK1/2) signaling pathways through physical interaction and stabilization of the ErbB family of growth factor RTKs ( Figure 8 ) [ 114 , 165 ].…”

“…Lung, liver, stomach, colorectal, prostate, breast, and cervical/uterine cancer are probably the most frequently diagnosed cancers recorded in economically developing countries. Medical breakthroughs to treat and prevent this disease are always in demand [ 4 , 5 , 6 ], and attention toward plant-derived compounds reduces the risk of side effects compared to current chemotherapy treatments. Drug resistance, and notably multidrug resistance (MDR), whose ultimate consequence is apoptosis resistance, has long been regarded as the most significant barrier in cancer therapy.…”

Identification of multiple novel genetic mechanisms that regulate chilling tolerance in Arabidopsis

“…Blast2GO was used to determine the function and localization of the candidate genes. Blast2GO is a widely used annotation platform that uses homology searches to associate sequences with Gene Ontology (GO) terms and other functional annotations ( Conesa et al., 2005 ; BioBam Bioinformatics, 2019 ; Sahoo et al., 2022 ). Blast2GO generated Gene Ontology annotations based on (a) Biological process, (b) Molecular Function, and (c) Cellular Component.…”

Canine chronic enteropathy—Current state-of-the-art and emerging concepts

“…Canine intestinal organoids derived from healthy dogs and dogs with chronic GI diseases have been recently investigated ( 232 – 236 ). In a seminal study, derivation of canine intestinal organoids was described using tissues obtained endoscopically from the duodenum, ileum, and colon of healthy adult dogs and dogs with idiopathic IBD or intestinal mast cell tumor ( 232 ).…”

“…Canine intestinal organoids derived from healthy dogs and dogs with chronic GI diseases have been recently investigated ( 232 – 236 ). In a seminal study, derivation of canine intestinal organoids was described using tissues obtained endoscopically from the duodenum, ileum, and colon of healthy adult dogs and dogs with idiopathic IBD or intestinal mast cell tumor ( 232 ). Using an optimized culture protocol, organoids were extensively investigated for their phenotypic characteristics using H&E histology, immunohistochemistry (IHC), RNA in situ hybridization (RNA-ISH), and transmission electron microscopy (TEM) for comparison to whole jejunal tissue.…”