Exosomal smRNA, a noninvasive biomarker for diagnosis of inflammatory bowel disease
Open Access
- Author:
- Manning, Sean Henry
- Graduate Program:
- Laboratory Animal Medicine
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- June 25, 2020
- Committee Members:
- Tiffany Lynn Whitcomb, Thesis Advisor/Co-Advisor
Yuka Imamura, Committee Member
Gregory Steven Yochum, Committee Member
Hannah Atkins, Committee Member
Ronald Paul Wilson, Program Head/Chair - Keywords:
- IL-10
Mouse
smRNA
miRNA
NGS
IBD
Colitis
Exosome - Abstract:
- Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract affecting over 3 million adults in the United States. Despite being widespread, reliable early diagnostic tests are not available. In order to remedy this, we evaluated exosomal small RNA (smRNA), specifically targeting microRNA (miRNA) and piRNA from the stool samples of IBD model mice as a potential diagnostic marker. Exosomes are a sub-type of extracellular nano-sized vesicles that mediate extracellular communication via transport of various biomolecules such as coding and non-coding RNAs (e.g., miRNA). The exosome communication process impacts several physiological and pathological pathways by modulating protein expression. Recently, investigation into the applicability of exosomal miRNA as diagnostic biomarkers has grown significantly. Here, we evaluated exosomal smRNA, specifically targeting miRNA, and piRNA from the stool samples of IBD model mice as potential markers of IBD. We used interleukin 10 knockout mice (IL-10KO), a validated model for IBD, and compared their fecal exosomal small RNA to that of wild type C57BL/6J (B6) mice. Stool samples were specifically chosen because they are readily available and collection is noninvasive. Feces were collected weekly for a total of 7 weeks from 28, conventionally housed, 4-week-old IL-10KO mice. Equal numbers of males (n=7), and females (n=7) were randomly assigned to each group. Additionally, a modified Crohn’s disease activity index was used to score each mouse’s clinical condition twice a week. At the end of the experimental period, the GI tract was collected, and disease severity scored. Histopathology showed a significant increase in inflammation and proliferation within the proximal and distal large intestines. In total, 12 smRNA’s were found that are modulated during the development of IBD in our mouse model. Their unique expression patter may help differentiate IBD from related diseases and allow for earlier and less invasive diagnosis.