Up-regulation of signal transducer and activator of transcription-3 is associated with aggravation of ulcerative colitis

Abstract 

Objective

The signal transducers and activators of transcription (STAT) family of proteins are intracellular signal transduction molecules involved in the expression of numerous proinflammatory genes in inflammatory cells. This study was executed to determine the association between the expression pattern of STAT-3 in the colonic mucosa of patients with ulcerative colitis (UC) and the progression of this disease.

Methods

We carried out the real-time reverse transcription-polymerase chain reaction (RT-PCR), Western-blot analysis and immunohistochemical staining to examine the expression of STAT-3 at both mRNA and protein levels in 25 patients with UC and 10 normal controls. The association between STAT-3 expression pattern and the severity of the disease was also analyzed.

Results

The expression of STAT-3 mRNA and protein in the ulcerated and inflamed colonic mucosa was significantly higher than that in the non-inflamed colonic mucosa (for mRNA: P = 0.001, 0.02 and for protein: P = 0.003, 0.03, respectively), but there was no statistically significant difference in the non-inflamed colonic mucosa of UC patients and normal controls (for mRNA: P = 0.062 and for protein: P = 0.063). Furthermore, immunohistochemical analysis showed that among the inactive, mild ∼ moderate, and severe colonic mucosae of UC patients, the positive rates of STAT-3 expression were 60.0%, 66.7%, and 88.9%, respectively.

Conclusion

Our study provides convincing evidence for the first time that the up-regulation of STAT-3 in colonic mucosa may be associated with the progression of human UC and STAT-3 may be a potential therapeutic target for this disease.

Keywords: Ulcerative colitis, Signal transducers and activators of transcription-3, Reverse transcription-polymerase chain reaction, Western-blot, Immunohistochemistry