Understanding epigenetic mechanism: a novel way to approach therapeutic targets for the treatment of colitis

Research output: Contribution to conferencePosterpeer-review

Abstract

Background: Chronic inflammatory bowel disease such as colitis is characterized by abdominal pain, for which pharmacological therapies are very limited. In addition, the excessive and exacerbated immune response within the gastrointestinal tract makes the underlying mechanisms of colitis more complex to understand. Numerous studies have shown that epigenetic regulation, especially DNA methylation, plays an important role in inflammatory modulation. Epigenetics is the study of changes in gene expression, which occurs without any changes in the DNA sequence. Previous studies have linked the Nerve growth factor (NGF), which plays an important role in inflammation and immune response, expression with neurogenic inflammation in various inflammatory animal models. Yet, the epigenetic mechanism for this NGF regulation is unexplored.

Aim: In this study, we evaluated the epigenetic mechanisms which regulate the gene expression of NGF during TNBS induced colitis in rats.

Method: Colitis was induced in 8-10 weeks old female Sprague-Dawley rats by infusing TNBS into the colon. The colon was collected after 24 hours of inflammation. Azacitidine (Aza) was pre- and co- administered to/with TNBS in the colon. Bisulfite converted DNA was used for Methylation-specific PCR (MSP) to analyze the DNA methylation patterns in the NGF promoter's CpG islands. RNA and protein expression of NGF was determined by qualitative, quantitative PCR, and immunoblot techniques.

Results & Conclusion: Our findings show altered NGF expression in the colon during TNBS induced colitis due to hypermethylation of CpG dinucleotides in the NGF promoter. Aza treatment mitigated this hypermethylation and reduced neurogenic inflammation in these animals suggesting NGF expression can be epigenetically regulated in neuroinflammation.
Original languageAmerican English
Pages70
StatePublished - 22 Feb 2021
EventOklahoma State University Center for Health Sciences Research Days 2021: Poster presentation - Oklahoma State University Center for Health Sciences Campus, Tulsa, United States
Duration: 22 Feb 202126 Feb 2021

Conference

ConferenceOklahoma State University Center for Health Sciences Research Days 2021
Country/TerritoryUnited States
CityTulsa
Period22/02/2126/02/21

Keywords

  • Inflammation
  • Chronic inflammatory bowel disease
  • Colitis
  • Nerve growth factor
  • Epigenetic regulation

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