Project R-15273

MicroRNA regulation of enteric glial cell reactivity in gastrointestinal health and disease. (Research)

Enteric glia, constituting the glial cell population of the enteric nervous system (ENS), are crucial for maintaining gastrointestinal (GI) homeostasis. These glial cells acquire a reactive phenotype in response to injury and inflammation, contributing to gut pathophysiology. Yet, the molecular underpinnings of enteric glia reactivity are unknown. Our preliminary data suggest the involvement of miR-146a-5p, a microRNA known for its role in GI diseases, including colorectal cancer (CRC). To elucidate the precise function of miR-146a-5p in enteric glia in GI health and disease, I will combine in vitro approaches and in vivo mouse models with investigation on human CRC specimens. These experiments promise to resolve the role of miR-146a-5p and its target interactions in enteric glial reactivity and maintenance of GI homeostasis and will clarify the impact of enteric glial miR-146a-5p on colorectal carcinogenesis. miR-146a-5p is anticipated to be a pivotal driver of enteric glial reactivity, a cornerstone of ENS-mediated GI inflammation and CRC. Therefore, this research will reveal whether targeting miR-146a-5p to modulate enteric glia reactivity has potential as a treatment strategy for GI disorders, holding promise for millions of patients in the future.

01 November 2024 - 31 October 2028