MIR-133A REGULATES THE DEVELOPMENT OF ULCERATIVE COLITIS THROUGH THE IL-6/STAT3 SIGNALING AXIS

To find new factors responsible for the development of ulcerative colitis (UC) in model rats to facilitate the development of new therapeutic strategies. Forty rats were separated into four groups, the control (Control), model (Model), negative control (NC) and antisense-miR-133 alpha treated (Treat) groups. UC was induced in rats, except those in the Normal group. Their mental statuses, body weights and bloody stools were scored. The colon tissues were further stained to determine and compare several pathological scores. The myeloperoxidase (MPO) activities were determined for the comparison of neutrophil infiltrations. We also probed the protein levels of STAT3 and TGF-beta 1 in the colon tissues using immunohistochemistry, and quantitated the transcripts of miR-133 alpha, STAT3, Foxp3 and RoRyt using qRT-PCR. Finally, the Th17 and Treg cells were counted with flow cytometry to analyze the balance between these two important components during immune response. miR-133 alpha was aberrantly upregulated in the rats with UC. Intracolonic injection of antisense-miR-133 alpha inhibitors could suppress the immune responses in the colons and reduce disease severity. The upregulated expression of miR-133 alpha was associated with enhanced STAT3 signaling and immune response in the colon tissues as suggested by the dysregulation of several key factors in this pathway and shifted balance between the Th17 and Treg cells. miR-133 alpha seems to regulate the development of UC through the STAT3 pathway, which can further affect the differentiation of Th17 cells. This microRNA is potentially a new drug target for the treatment of UC.