scholarly journals Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1078 ◽  
Author(s):  
Jesus Cosin-Roger ◽  
Francisco Canet ◽  
Dulce C. Macias-Ceja ◽  
Laura Gisbert-Ferrándiz ◽  
Dolores Ortiz-Masiá ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Fibrosis ◽  
Murine Colitis ◽  
Pharmacological Stimulation ◽  
Primary Fibroblasts ◽  
Potential Strategy ◽  
Autophagy Inhibition ◽  
Stimulation Of ◽  
Inflammatory Effect

We recently observed reduced autophagy in Crohn’s disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn’s disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis.

scholarly journals IL-10 Treatment Is Associated with Prohibitin Expression in the Crohn’s Disease Intestinal Fibrosis Mouse Model

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
C. Yuan ◽  
W.-X. Chen ◽  
J.-S. Zhu ◽  
N.-W. Chen ◽  
Y.-M. Lu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Interleukin 10 ◽  
Colon Tissue ◽  
Intestinal Fibrosis ◽  
Murine Colitis ◽  
Inflammatory Bowel

Prohibitin, which can inhibit oxidative stress and mitochondrial dysfunction, has been shown to have significant anti-inflammatory activities. Here, we investigate the effects of altering prohibitin levels in affected tissues in the interleukin-10 knockout (IL-10KO) mouse model with intestinal fibrosis. The aim of this study is to investigate the effects of IL-10 on prohibitin and the role of prohibitin in intestinal fibrosis of murine colitis. After the mice were treated with IL-10, prohibitin expression and localization were evaluated in IL-10KO and wild-type (WT, 129/SvEv) mice. The colon tissue was then investigated and the potential pathogenic molecular mechanisms were further studied. Fluorescence-based quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry assays revealed a significant upregulation of prohibitin with IL-10 treatment. Furthermore, IL-10 decreases inflammatory cytokines and TGF-β1 in the IL-10KO model of Crohn’s disease and demonstrates a promising trend in decreasing tissue fibrosis. In conclusion, we hypothesize that IL-10 treatment is associated with increased prohibitin and would decrease inflammation and fibrosis in an animal model of Crohn’s disease. Interestingly, prohibitin may be a potential target for intestinal fibrosis associated with inflammatory bowel disease (IBD).

scholarly journals Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Fan Zhao ◽  
Tao Zheng ◽  
Wenbin Gong ◽  
Jie Wu ◽  
Haohao Xie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extracellular Vesicles ◽  
Intestinal Inflammation ◽  
Therapeutic Effects ◽  
Murine Colitis ◽  
Sting Pathway ◽  
Deficient Mice

AbstractCrohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

scholarly journals IL-17 Promotes HSP47 Expression and Intestinal Fibrosis in Crohn's Disease

2011 ◽  
Vol 140 (5) ◽  
pp. S-493 ◽  
Author(s):  
Yusuke Honzawa ◽  
Hiroshi Nakase ◽  
Kayoko Matsumura ◽  
Shuji Yamamoto ◽  
Norimitsu Uza ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Fibrosis
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