Aberrant regenerating islet-derived protein 3 (REG3) expression is an early indicator of colonic dysplasia in heterogeneous nuclear ribonucleoprotein (HNRNP I) knockout mice

Regenerating islet-derived protein 3 (REG3) acts as multifunctional secretory molecules with pro-proliferative, anti-inflammatory, antimicrobial, and probably cancer-promoting effects. Here, knockout mice with an intestinal epithelial cell (IEC)-specific Hnrnp I gene (KO) ablation were examined, which exhibited an increased risk of developing spontaneous colitis. In this study, we demonstrated that Hnrnp I knockout in mouse intestinal epithelial cells resulted in hyperactive NF-κB signaling, which directly or indirectly downregulated the expression of Reg3b and Reg3g mRNA. We also observed that Hnrnp I knockout in mouse intestinal epithelial cells increased the expression of inflammatory and immune-associated chemokines, including Cxcl9, Cxcl10, Ccl6, and Ccl9. Among them, Cxcl9, Cxcl10, and Ccl9 had similar distribution patterns to Reg3b and Reg3g. Additionally, colonic dysplasia, as a common feature, has been identified in KO mice. We found significant upregulation of REG3B and REG3G protein expression in colonic dysplasia regions in KO mice compared to adjacent normal tissue, indicating that REG3 may serve as a response indicator of colonic dysplasia and an early warning of possible cancer development. The co-localization of GATA3-positive immunofluorescent signals with high levels of REG3 protein expression and colonic dysplasia, along with the identification of GATA3 binding sites in the putative promoter region of the mouse Reg3b gene DNA sequence, collectively indicate the potential regulatory and synergistic role of GATA3 in the development of colonic dysplasia involving REG3. Overall, these findings provide compelling evidence that REG3 has significant potential as an indication for colonic dysplasia.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Liang, Siyuan

Contributors dc:contributor

• Pan, Yuan-Xiang
• Chen, Hong
• Swanson, Kelly S.

• Mice
• Regenerating Islet-derived (reg) Gene
• Intestinal Epithelial Cell-specific Hnrnp I Knockout
• Colonic Dysplasia

Statement dc:rights

• Copyright 2023 Siyuan Liang

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121278

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121278