scholarly journals The ESRP1-GPR137 axis contributes to intestinal pathogenesis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lukas Franz Mager ◽  
Viktor Hendrik Koelzer ◽  
Regula Stuber ◽  
Lester Thoo ◽  
Irene Keller ◽  
...  
Keyword(s):  
Critical Role ◽  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Regulator Protein ◽  
Intestinal Pathology ◽  
Splicing Regulator ◽  
Inflammatory Bowel ◽  
Intestinal Barrier Integrity ◽  
Increased Susceptibility

Aberrant alternative pre-mRNA splicing (AS) events have been associated with several disorders. However, it is unclear whether deregulated AS directly contributes to disease. Here, we reveal a critical role of the AS regulator epithelial splicing regulator protein 1 (ESRP1) for intestinal homeostasis and pathogenesis. In mice, reduced ESRP1 function leads to impaired intestinal barrier integrity, increased susceptibility to colitis and altered colorectal cancer (CRC) development. Mechanistically, these defects are produced in part by modified expression of ESRP1-specific Gpr137 isoforms differently activating the Wnt pathway. In humans, ESRP1 is downregulated in inflamed biopsies from inflammatory bowel disease patients. ESRP1 loss is an adverse prognostic factor in CRC. Furthermore, generation of ESRP1-dependent GPR137 isoforms is altered in CRC and expression of a specific GPR137 isoform predicts CRC patient survival. These findings indicate a central role of ESRP1-regulated AS for intestinal barrier integrity. Alterations in ESRP1 function or expression contribute to intestinal pathology.

Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

2017 ◽  
Vol 12 (4) ◽  
pp. 923-935 ◽  
Author(s):  
Fredrik E.O. Holmberg ◽  
Jannie Pedersen ◽  
Peter Jørgensen ◽  
Christoffer Soendergaard ◽  
Kim B. Jensen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cell ◽  
Bowel Disease ◽  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Inflammatory Bowel ◽  
Intestinal Barrier Integrity

Role of NHE3 in the Maintenance of Intestinal Barrier Integrity in IL-10-Deficient Mice

2011 ◽  
Vol 140 (5) ◽  
pp. S-634-S-635
Author(s):  
Claire B. Larmonier ◽  
Daniel Laubitz ◽  
Alexis L. Bucknam ◽  
Robert D. Thurston ◽  
Faihza M. Hill ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Deficient Mice

scholarly journals The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0220642 ◽  
Author(s):  
Yuliia Holota ◽  
Taisa Dovbynchuk ◽  
Izumi Kaji ◽  
Igor Vareniuk ◽  
Natalia Dzyubenko ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Antibiotic Therapy ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Long Term Consequences

Role of defective methylation reactions in ethanol-induced dysregulation of intestinal barrier integrity

2015 ◽  
Vol 96 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Paul G. Thomes ◽  
Natalia A. Osna ◽  
Sarah M. Bligh ◽  
Dean J. Tuma ◽  
Kusum K. Kharbanda
Keyword(s):  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity

HDAC as Versatile Regulators of the Intestinal Barrier Integrity and Epithelial Regeneration in Inflammatory Bowel Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S967
Author(s):  
Marie Friedrich ◽  
Julia Ganther ◽  
Tilman Breiderhoff ◽  
Rita Rosenthal ◽  
Rainer Glauben ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Epithelial Regeneration ◽  
Inflammatory Bowel ◽  
Intestinal Barrier Integrity

scholarly journals Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice

2010 ◽  
Vol 207 (8) ◽  
pp. 1617-1624 ◽  
Author(s):  
Athena Chalaris ◽  
Nina Adam ◽  
Christian Sina ◽  
Philip Rosenstiel ◽  
Judith Lehmann-Koch ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Intestinal Barrier ◽  
Systemic Availability ◽  
Epidermal Growth ◽  
Targeting Strategy ◽  
Necrosis Factor ◽  
Increased Susceptibility

The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17ex/ex were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17ex/ex mice was normal, ADAM17ex/ex mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target.

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