scholarly journals miR-200b inhibits TGF-β1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells

2013 ◽  
Vol 4 (3) ◽  
pp. e541-e541 ◽  
Author(s):  
Y Chen ◽  
Y Xiao ◽  
W Ge ◽  
K Zhou ◽  
J Wen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Tgf Β1

scholarly journals A KDM4-DBC1-SIRT1 Axis Contributes to TGF-b Induced Mesenchymal Transition of Intestinal Epithelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Baoyu Chen ◽  
Wenhui Dong ◽  
Tinghui Shao ◽  
Xiulian Miao ◽  
Yan Guo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Class Iii ◽  
Benzene Sulfonic Acid ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Lysine Deacetylase ◽  
Bowel Diseases

Intestinal fibrosis is one of the common pathophysiological processes in inflammatory bowel diseases (IBDs). Previously it has been demonstrated that epithelial-mesenchymal transition (EMT) can contribute to the development of intestinal fibrosis. Here we report that conditional ablation of SIRT1, a class III lysine deacetylase, in intestinal epithelial cells exacerbated 2, 4, 6-trinitro-benzene sulfonic acid (TNBS) induced intestinal fibrosis in mice. SIRT1 activity, but not SIRT1 expression, was down-regulated during EMT likely due to up-regulation of its inhibitor deleted in breast cancer 1 (DBC1). TGF-β augmented the recruitment of KDM4A, a histone H3K9 demethylase, to the DBC1 promoter in cultured intestinal epithelial cells (IEC-6) leading to DBC1 trans-activation. KDM4A depletion or inhibition abrogated DBC1 induction by TGF-β and normalized SIRT1 activity. In addition, KDM4A deficiency attenuated TGF-β induced EMT in IEC-6 cells. In conclusion, our data identify a KDM4-DBC1-SIRT1 pathway that regulates EMT to contribute to intestinal fibrosis.

scholarly journals Herbs-Partitioned Moxibustion Combined with Acupuncture Inhibits TGF-β1-Smad-Snail-Induced Intestinal Epithelial Mesenchymal Transition in Crohn’s Disease Model Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yin Shi ◽  
Tao Li ◽  
Jing Zhou ◽  
Yuwei Li ◽  
Liu Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Cell Marker ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis

Crohn’s disease may cause excessive damage and repair in the intestinal epithelium due to its chronic relapsing intestinal inflammation. These factors may initiate the TGF-β 1-Smad pathway to activate the transcription factor of Snail, and the Snail-mediated pathway promotes the transformation of intestinal epithelial cells to mesenchymal cells, leading to intestinal fibrosis. Acupuncture and moxibustion have been demonstrated to prevent intestinal fibrosis in Crohn’s disease. However, it is not clear whether acupuncture and moxibustion can inhibit intestinal epithelial mesenchymal transformation in Crohn’s disease by affecting the TGF-β 1-Smad-Snail pathway. This study indicated that abnormal increased expressions of TGFβ1, TβR2, Smad3, and Snail were significantly downregulated by herbs-partitioned moxibustion at Tianshu (ST25) and Qihai (RN6) and acupuncture at Zusanli (ST36) and Shangjuxu (ST37). In addition, protein and mRNA levels of E-cadherin, the epithelial cell marker, were significantly increased. Protein and mRNA levels of fibronectin, the mesenchymal cell marker, were decreased in the intestinal tissue. Moreover, the number of mesenchymal cells in the intestinal mucosa can be reversely transformed to intestinal epithelial cells. Therefore, herbs-partitioned moxibustion combined with acupuncture can prevent intestinal epithelial mesenchymal transition by inhibiting abnormal expression of TGFβ1, TβR2, Smad3, and Snail in the TGF-β1-Smad-Snail pathway in Crohn’s disease.

scholarly journals The Crosstalk between Nrf2 and TGF-β1 in the Epithelial-Mesenchymal Transition of Pancreatic Duct Epithelial Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132978 ◽  
Author(s):  
Sarah Arfmann-Knübel ◽  
Birte Struck ◽  
Geeske Genrich ◽  
Ole Helm ◽  
Bence Sipos ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pancreatic Duct ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tgf Β1

Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial cells

2007 ◽  
Vol 293 (1) ◽  
pp. L212-L221 ◽  
Author(s):  
Shilpa Vyas-Read ◽  
Philip W. Shaul ◽  
Ivan S. Yuhanna ◽  
Brigham C. Willis
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cells ◽  
No Production ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Oxide Synthase ◽  
Tgf Β1

Patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF) and bronchopulmonary dysplasia (BPD), suffer from lung fibrosis secondary to myofibroblast-mediated excessive ECM deposition and destruction of lung architecture. Transforming growth factor (TGF)-β1 induces epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) to myofibroblasts both in vitro and in vivo. Inhaled nitric oxide (NO) attenuates ECM accumulation, enhances lung growth, and decreases alveolar myofibroblast number in experimental models. We therefore hypothesized that NO attenuates TGF-β1-induced EMT in cultured AEC. Studies of the capacity for endogenous NO production in AEC revealed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) are expressed and active in AEC. Total NOS activity was 1.3 pmol·mg protein−1·min−1 with 67% derived from eNOS. TGF-β1 (50 pM) suppressed eNOS expression by more than 60% and activity by 83% but did not affect iNOS expression or activity. Inhibition of endogenous NOS with l-NAME led to spontaneous EMT, manifested by increased α-smooth muscle actin (α-SMA) expression and a fibroblast-like morphology. Provision of exogenous NO to TGF-β1-treated AEC decreased stress fiber-associated α-SMA expression and decreased collagen I expression by 80%. NO-treated AEC also retained an epithelial morphology and expressed increased lamellar protein, E-cadherin, and pro-surfactant protein B compared with those treated with TGF-β alone. These findings indicate that NO serves a critical role in preserving an epithelial phenotype and in attenuating EMT in AEC. NO-mediated regulation of AEC fate may have important implications in the pathophysiology and treatment of diseases such as IPF and BPD.

scholarly journals Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1104 ◽  
Author(s):  
Dolores Ortiz-Masiá ◽  
Laura Gisbert-Ferrándiz ◽  
Cristina Bauset ◽  
Sandra Coll ◽  
Céline Mamie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Wnt Signaling ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Fistula Tract ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Ht29 Cells

The pathogenesis of Crohn’s disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn’s disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis. EMT, as increased expression of Snail1, Snail2 and vimentin and reduction in E-cadherin, was analyzed in tissues and succinate-treated HT29 cells. The role played by SUCNR1 was studied by silencing its gene. Succinate levels and SUCNR1 expression are increased in B3-CD patients and correlate with EMT markers. SUCNR1 is detected in transitional cells lining the fistula tract and in surrounding mesenchymal cells. Grafts from wild type (WT) mice present increased succinate levels, SUCNR1 up-regulation and EMT activation, effects not observed in SUCNR1−/− tissues. SUCNR1 activation induces the expression of Wnt ligands, activates WNT signaling and induces a WNT-mediated EMT in HT29 cells. In conclusion, succinate and its receptor are up-regulated around CD-fistulas and activate Wnt signaling and EMT in intestinal epithelial cells. These results point to SUCNR1 as a novel pharmacological target for fistula prevention.

Sign in / Sign up

Export Citation Format

Share Document