Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-01169-6
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [U1501224, 81370511]
- Natural Science Foundation of Guangdong Province [S2013010016541]
- Science and Technology Planning Projects of Guangdong Province [2016A020216014]
- Science and Technology Planning Projects of Guangzhou City [201604020118, 201604020002]
- Fundamental Research Funds for the Central Universities [15ykpy24]
Ask authors/readers for more resources
COX-1/PGE(2) is an important protective mediator in ulcerative colitis ( UC). beta-arrestin1 ( beta-arr1), which acts as a scaffold protein, is involved in PGE(2)-mediated signaling pathways. However, the interaction between PGE(2) and beta-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE(2) were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE(2) treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium ( DSS)-induced colitis in wild-type ( WT) mice. Following DSS-induced injury, beta-arr1 deficient mice showed increased signs of colitis compared to beta-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in beta-arr1 deficient mice. In parallel, HCT116 cells transfected with beta-arr1 siRNA were examined in the presence or absence of PGE(2) in vitro. PGE(2) treatment in the beta-arr1 WT/KO DSS model and beta-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated beta-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE(2)/EP4 upregulates the beta-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE(2) in UC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available