Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

Farooq, Shukkur M.; Hou, Yuning; Li, Hainan; O’Meara, Megan M.; Wang, Yihan; Li, Chunying; Wang, Jiemei

doi:10.1007/s10620-018-5216-z

Cited by 52 publications

(51 citation statements)

References 32 publications

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“…For example, the GPR35 promoter was found to be the most hypermethylated promoter in sNEC colon compared to non-NEC colon. GPR35 is highly expressed in immune and intestinal epithelial cells, and its loss of function has been shown to promote colitis in an experimental animal model [29]. Similarly, the third most hypermethylated promoter in our data when comparing sNEC colon to control is located upstream of ring finger protein 186 (RNF186), which maintains gut homeostasis by controlling ER stress in colonic epithelium [30].…”

Section: Discussionsupporting

confidence: 55%

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

et al. 2020

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Background Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation. Methods Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data. Results We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation. Conclusions We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.

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Section: Discussionsupporting

confidence: 55%

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

et al. 2020

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“…A genome-wide association study has identified a single nucleotide polymorphism in GPR35 among UC patients [29], potentially linking the regulation of GPR35 to IBD. Recent studies have suggested GPR35 participates in mucosal repair regulation [30,31]. A role of GPR87 in cancer growth and metastasis is emerging too [32,33].…”

Section: Lpa Metabolism and Signalingmentioning

confidence: 99%

Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

Yun

2019

Cancers

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The intestinal epithelium interacts dynamically with the immune system to maintain its barrier function to protect the host, while performing the physiological roles in absorption of nutrients, electrolytes, water and minerals. The importance of lysophosphatidic acid (LPA) and its receptors in the gut has been progressively appreciated. LPA signaling modulates cell proliferation, invasion, adhesion, angiogenesis, and survival that can promote cancer growth and metastasis. These effects are equally important for the maintenance of the epithelial barrier in the gut, which forms the first line of defense against the milieu of potentially pathogenic stimuli. This review focuses on the LPA-mediated signaling that potentially contributes to inflammation and tumor formation in the gastrointestinal tract.

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“…The pathological changes in the DSS-induced IBD model are similar to human UC. Thus, it is an ideal model that has been widely used to study the mechanism of UC and for screening potential drugs ( Farooq et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis

Han

Sun

et al. 2021

PeerJ

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Background Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of Lithospermum erythrorhizon have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC. Methods In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight. Results Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues. Conclusions Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.

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Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

Abstract: Our experimental data suggest that lack of GPR35 resulted in worsened disease outcome in DSS-induced experimental colitis, indicating that GPR35 could play a crucial role in protecting from colonic inflammation and serve as a therapeutic target.

Cited by 52 publications

References 32 publications

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis

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