Blockade of STAT3 by Antisense Oligonucleotide in TNBS-induced Murine Colitis

Overview

Journal Int J Colorectal Dis

Specialties Gastroenterology
General Surgery

Date 2006 Nov 8

PMID 17089128

Citations 13

Authors

Aiping Bai

Pinjin Hu

Jie Chen

Xin Song

Wei Chen

Wenxin Peng

Zhirong Zeng

Xiang Gao

Affiliations

Soon will be listed here.

Abstract

Background And Aims: The expression of signal transducers and activators of transcription 3 (STAT3) is increased in Crohn's disease (CD), and nuclear translocated STAT3 is also found in the disease. However, the role of STAT3 protein on the pathogenesis of CD is not clear. This study was executed to investigate the role of STAT3 protein on the pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis, the pathogenesis of which is CD-like.

Methods: TNBS-induced colitis was produced, and STAT3 antisense oligonucleotide was administrated intracolonically during the early phase of colitis. The mice were killed 7 days later, and the expressions of STAT3 and phosphorylated STAT3 were identified by Western blot and immunofluorescence. The lamina propria mononuclear cells (LPMCs) were isolated freshly, and the percent of cell death and the expressions of Bcl-2 and Bax in LPMCs were evaluated. Colonic tissue damage and the production of inflammatory cytokines were measured also.

Results: Administration of STAT3 antisense oligonucleotide effectively inhibited STAT3 expression and phosphorylation in inflamed colonic mucosa of colitis. The mice that were administered STAT3 antisense oligonucleotide showed less colonic tissue damage with decreased production of inflammatory cytokines such as TNF-alpha and INF-gamma in mucosa compared with that of those TNBS-induced colitis. Administration of STAT3 antisense oligonucleotide successfully induced apoptosis of LPMCs and counteracted the unbalanced expressions of Bcl-2 and Bax in LPMCs from colitis.

Conclusions: STAT3 activation may play an important role in the inflammatory process of TNBS-induced colitis, and inhibiting STAT3 activation during the early phase of the inflammatory response may have a beneficial effect on the colitis.

Citing Articles

Investigating the association between the tissue expression of miRNA-101, JAK2/STAT3 with TNF-α, IL-6, IL-1β, and IL-10 cytokines in the ulcerative colitis patients.

Voshagh Q, Anoshiravani A, Karimpour A, Goodarzi G, Tehrani S, Tabatabaei-Malazy O Immun Inflamm Dis. 2024; 12(3):e1224.

PMID: 38517042 PMC: 10958669. DOI: 10.1002/iid3.1224.

Phytochemicals Targeting JAK-STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models.

Moon S, Kim K, Yoo J, Lee J, Hwangbo C Molecules. 2021; 26(9).

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Targeting key transcriptional factor STAT3 in colorectal cancer.

Chalikonda G, Lee H, Sheik A, Huh Y Mol Cell Biochem. 2021; 476(9):3219-3228.

PMID: 33866491 DOI: 10.1007/s11010-021-04156-8.

Targeting STAT3 with Proteolysis Targeting Chimeras and Next-Generation Antisense Oligonucleotides.

Shiah J, Grandis J, Johnson D Mol Cancer Ther. 2020; 20(2):219-228.

PMID: 33203730 PMC: 7888537. DOI: 10.1158/1535-7163.MCT-20-0599.

JAK-STAT pathway targeting for the treatment of inflammatory bowel disease.

Salas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S Nat Rev Gastroenterol Hepatol. 2020; 17(6):323-337.

PMID: 32203403 DOI: 10.1038/s41575-020-0273-0.

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