Reciprocal Regulation Between Smad7 and Sirt1 in the Gut

Frontiers in Immunology
Silvia SeddaGiovanni Monteleone

Abstract

In inflammatory bowel disease (IBD) mucosa, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine transforming growth factor-β1, due to post-transcriptional mechanisms that enhance Smad7 acetylation status thus preventing ubiquitination-mediated proteosomal degradation of the protein. IBD-related inflammation is also marked by defective expression of Sirt1, a class III NAD+-dependent deacetylase, which promotes ubiquitination-mediated proteosomal degradation of various intracellular proteins and triggers anti-inflammatory signals. The aim of our study was to determine whether, in IBD, there is a reciprocal regulation between Smad7 and Sirt1. Smad7 and Sirt1 were examined in mucosal samples of IBD patients and normal controls by Western blotting and immunohistochemistry, and Sirt1 activity was assessed by a fluorimetric assay. To determine whether Smad7 is regulated by Sirt1, normal or IBD lamina propria mononuclear cells (LPMC) were cultured with either Sirt1 inhibitor (Ex527) or activator (Cay10591), respectively. To determine whether Smad7 controls Sirt1 expression, ex vivo organ cultures of IBD mucosal explants were treated with Smad7 sense or antisense oligonucleotide. Moreover, Sirt1 exp...Continue Reading

References

May 23, 1998·Annual Review of Immunology·J J Letterio, A B Roberts
Aug 24, 2001·The Journal of Clinical Investigation·G MonteleoneT T MacDonald
Nov 1, 2002·Molecular Cell·Eva GrönroosJohan Ericsson
Jul 24, 2003·Nature Reviews. Immunology·Gerd Bouma, Warren Strober
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susan C McKarnsNorbert E Kaminski
Sep 15, 2004·Trends in Immunology·Giovanni MonteleoneThomas T MacDonald
Feb 3, 2005·Gastroenterology·Taeko DohiItaru Kojima
Nov 16, 2005·Gastroenterology·Giovanni MonteleoneThomas T MacDonald
Mar 3, 2007·The Journal of Clinical Investigation·Warren StroberPeter Mannon
Dec 23, 2008·Mucosal Immunology·G MonteleoneT T MacDonald
Feb 5, 2009·Gastroenterology·Massimo C FantiniGiovanni Monteleone
Sep 5, 2009·The Journal of Clinical Investigation·Jinping ZhangDeyu Fang

❮ Previous
Next ❯

Citations

Oct 22, 2020·Critical Reviews in Biochemistry and Molecular Biology·Charlotte de Ceuninck van CapellePeter Ten Dijke
Apr 20, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Irene MarafiniGiovanni Monteleone
May 1, 2021·International Journal of Molecular Sciences·Edoardo TronconeGiovanni Monteleone
May 25, 2021·Frontiers in Chemistry·Di ZhouJingchao Lin

❮ Previous
Next ❯

Methods Mentioned

BETA
antisense oligonucleotide
acetylation
biopsies
biopsy
Assay
electrophoresis
Transgenic
flow cytometry
ubiquitination
immunoprecipitation

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here