4.7 Article

Activation of sirtuin 1 by catalpol-induced down-regulation of microRNA-132 attenuates endoplasmic reticulum stress in colitis

Journal

PHARMACOLOGICAL RESEARCH
Volume 123, Issue -, Pages 73-82

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2017.05.030

Keywords

Sirtuin 1; MicroRNA-132; Inflammatory bowel disease; Endoplasmic reticulum stress; Catalpol; Colitis

Funding

  1. National Natural Science Foundation of China [81600440]
  2. Dalian Municipal Medical Research Foundation

Ask authors/readers for more resources

Defective expression of NAD-dependent protein deacetylase sirtuin 1 (SIRT1) triggers endoplasmic reticulum (ER) stress and epithelial cell apoptosis in inflammatory bowel disease. MicroRNA-132 (miR-132) has been shown to regulate inflammatory processes through down-regulating SIRT1. Catalpol is a potential antioxidant and anti-apoptotic agent in inflammatory disease. This study aimed to investigate the signaling mechanisms underlying catalpol-induced SIRT1 activation and inhibition of ER stress in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. miR-132 expression was measured by quantitative real-time polymerase chain reaction and in situ hybridization, and the regulation of SIRT1 by miR-132 was examined by dual luciferase reporter assay. Protein expression related to ER stress and apoptosis was measured by western blotting. The ER stress marker proteins ATF6, CHOP, and caspasel 2, and acetylation of heat-shock factor-1 were increased in colitis and these increases were significantly reversed by catalpol, while the colitis-induced reduction in GRP78 was also reversed by catalpol. The inhibition of ER stress by catalpol was significantly inhibited by small interfering RNA targeting SIRT1 or miR-132. Moreover, other colitis symptoms including infiltration of inflammatory cells, cytokine profiles, oxidative responses, and epithelial cell apoptosis were also significantly decreased by catalpol. Mechanistically, the defective expression of SIRT1 in colitis was significantly counteracted by catalpol, while miR-132, which is a negative targeting regulator of SIRT1, was confirmed as the potential target of catalpol. These results support a link between ER stress and the miR-132/SIRT1/heat-shock factor-1 signaling pathway, and the modulation of this pathway by catalpol in colitis. (C) 2017 Elsevier Ltd. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available