Abstract:
AIM:To determine if exacerbation of pre-existing chronic colitis in Winnie (Muc2 mutant) mice induces colonic dysplasia. METHODS:Winnie mice and C57BL6 as a genotype control, were administered 1% w/v dextran sulphate sodium (DSS) orally, followed by drinking water alone in week-long cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon. Epithelial cell proliferation was assessed using Ki67 and aberrant β-catenin signalling assessed with enzyme-based immunohistochemistry. Extracted RNA from colonic segments was used for the analysis of gene expression using real-time quantitative PCR. Finally, the distribution of Cxcl5 was visualised using immunohistochemistry. RESULTS:Compared to controls, Winnie mice exposed to three cycles of DSS displayed inflammation mostly confined to the distal-mid colon with extensive mucosal hyperplasia and regenerative atypia resembling epithelial dysplasia. Dysplasia-like changes were observed in 100% of Winnie mice exposed to DSS, with 55% of these animals displaying changes similar to high-grade dysplasia, whereas high-grade changes were absent in wild-type mice. Occasional penetration of the muscularis mucosae by atypical crypts was observed in 27% of Winnie mice after DSS. Atypical crypts however displayed no evidence of oncogenic nuclear β-catenin accumulation, regardless of histological severity. Expression of Cav1, Trp53 was differentially regulated in the distal colon of Winnie relative to wild-type mice. Expression of Myc and Ccl5 was increased by DSS treatment in Winnie only. Furthermore, increased Ccl5 expression correlated with increased complexity in abnormal crypts. While no overall difference in Cxcl5 mucosal expression was observed between treatment groups, epithelial Cxcl5 protein appeared to be diminished in the atypical epithelium. CONCLUSION:Alterations to the expression of Cav1, Ccl5, Myc and Trp53 in the chronically inflamed Winnie colon may influence the transition to dysplasia.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Randall-Demllo S,Fernando R,Brain T,Sohal SS,Cook AL,Guven N,Kunde D,Spring K,Eri Rdoi
10.3748/wjg.v22.i37.8334subject
Has Abstractpub_date
2016-10-07 00:00:00pages
8334-8348issue
37eissn
1007-9327issn
2219-2840journal_volume
22pub_type
杂志文章abstract:AIM:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with undifferentiated-type histology. METHODS:A systematic literature review was conducted using the core databases. Complete resection, curative resection, en bloc resection, recurrence and adverse event r...
journal_title:World journal of gastroenterology
pub_type: 杂志文章,meta分析,评审
doi:10.3748/wjg.v21.i19.6032
更新日期:2015-05-21 00:00:00
abstract::Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma (HCC). Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats...
journal_title:World journal of gastroenterology
pub_type: 社论
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doi:10.3748/wjg.v19.i11.1718
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journal_title:World journal of gastroenterology
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pub_type: 临床试验,杂志文章
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v19.i36.6084
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v19.i16.2492
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pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.15.3684
更新日期:2009-08-07 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v24.i35.4061
更新日期:2018-09-21 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2007-12-14 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 临床试验,杂志文章
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更新日期:2005-10-14 00:00:00
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pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v21.i47.13352
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journal_title:World journal of gastroenterology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2015-03-14 00:00:00