MicroRNA-320a Strengthens Intestinal Barrier Function and Follows the Course of Experimental Colitis.
Inflammatory bowel disease is a chronic-remittent disorder with the risk of disabling complications due to uncontrolled inflammation. Accurate biomarkers are needed to noninvasively monitor the disease course to tailor therapy. We evaluated the potential of the specific microRNA (miR)-320a to monitor disease activity in experimental colitis or patients with Crohn's disease and investigated its functional role in intestinal epithelial barrier formation.



The impact of miR-320a on intestinal barrier function was tested in vitro in T84 epithelial cells by transepithelial resistance measurement and quantitative real-time polymerase chain reaction analysis on inflammatory and microbial stimulation. Experimental colitis was studied in dextran sodium sulfate colitis, T-cell transfer colitis, and IL-10 mice. Disease course was monitored by body weight measurement, colonoscopy, and histological examination. MiR-320a expression during inflammation was assessed in T84 cells, murine blood, and colonic tissue and in peripheral blood from patients with Crohn's disease with active or quiescent disease.



MiR-320a transfection of T84 cells reinforced barrier integrity reflected by increased transepithelial resistance (P < 0.01) and inhibited barrier-destructive enteropathogenic Escherichia coli effects resulting in increased tight junction protein JAM-A expression (P = 0.02) and decrease of barrier integrity-destabilizing miR-320a target PPP2R5B (P < 0.001). Tumor necrosis factor-α and interleukin-1β stimulation increased a miR-320a epxression in T84 cells. MiR-320a level was increased in blood samples from colitic mice and patients with Crohn's disease showing a strong correlation with disease activity (r = 0.67).



MiR-320a strengthens intestinal barrier function in vitro and has the potential to monitor disease activity of colitic mice. Future studies are needed to further evaluate the potential of miR-320a in patients with inflammatory bowel disease.
*Department of Medicine B, University Hospital Münster, Münster, Germany; †Institute of Palliative Care, University Hospital Münster, Münster, Germany; ‡Center for Molecular Biology of Inflammation, Institute of Infectiology, University of Münster, Münster, Germany; and §Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Friederike
F
Cordes
Markus
M
Brückner
Philipp
P
Lenz
Katharina
K
Veltman
Rainer
R
Glauben
Britta
B
Siegmund
Karin
K
Hengst
Markus Alexander
MA
Schmidt
Christoph
C
Cichon
Dominik
D
Bettenworth
D000328:Adult; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate