Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn’s disease

Ardizzone, Sandro; Bevivino, Gerolamo; Monteleone, Giovanni

doi:10.1177/1756283x16636781

Cited by 38 publications

(32 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…. Notably, enhancing TGF‐β signaling with Smad7 antisense nucleotides is a promising new therapeutic approach for IBD patients , and this would be a relevant setting to assess Th1‐to‐Th17‐cell conversion. However, since it is currently unclear whether Th1‐derived Th17 cells have the same pathogenic potential as conventional Th17 cells, any ensuing effects of Th1‐to‐Th17‐cell conversion on intestinal inflammation are difficult to predict.…”

Section: A Novel Pathway To Generate Th17 Cellsmentioning

confidence: 99%

Reverse plasticity: TGF‐β and IL‐6 induce Th1‐to‐Th17‐cell transdifferentiation in the gut

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: A Novel Pathway To Generate Th17 Cellsmentioning

confidence: 99%

Reverse plasticity: TGF‐β and IL‐6 induce Th1‐to‐Th17‐cell transdifferentiation in the gut

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The MohanKumar K group proposed that, in human necrotizing enterocolitis macrophages, increased SMAD7 expression augmented nuclear factor-kappa B (NF-κB) activation and cytokine production via increasing the expression of IKK-α [20]. Zorzi F et al and Ardizzone S et al both illustrated that, in human inflammatory bowel tissue, interrupting SMAD7 inhibits the inflammation action [21,22].…”

Section: Discussionmentioning

confidence: 99%

Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7

Zheng

Feng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Aortic stenosis caused by leaflet calcification in the bicuspid aortic valve (BAV) is more accelerative than that in the tricuspid aortic valve (TAV). is downregulated more in stenotic than in insufficient BAVs, but its expression in BAVs compared with TAVs is unclear. We aimed to investigate the roles of miR-195 and its calcification-related target SMAD7 in stenotic BAVs compared with those in TAVs. Methods: Twenty-one stenotic BAV and 29 TAV samples were collected from surgical patients and examined for the expression of miR-195 and SMAD7 by RT-PCR. The samples were also assessed by western blotting and immunohistochemistry for the functional protein alteration associated with calcification. Dual-luciferase assay was performed to determine the putative target of miR-195 before the effects of miR-195 expression on osteogenic progression was demonstrated in cultured porcine valve interstitial cells (VICs). Results: Compared with TAV, the expression of miR-195 was remarkably lower in the BAV leaflet with higher expression of SMAD7, which was then validated as a direct target of miR-195. Their negative correlation was then confirmed in cultured VICs. Under an osteogenic environment, the cellular calcification was promoted in miR-195-repressed VICs expressing higher BMP-2 and Runx2 and higher activity of MMP-2 compared with the controls. Finally, higher MMP-2 and MMP-9 expression and more collagen distribution were observed in BAV than TAV samples. Conclusions: miR-195 is downregulated more in stenotic BAV than TAV in this study. The downregulation of miR-195 is associated with valvular calcification via targeting SMAD7, which promotes the remodeling of the extracellular matrix.

show abstract

“…The Mongersen showed clinical remission (55% with 40mg and 65% with 160mg) as compared to placebo (10%; p<0.001). 120,121 Currently, the two-randomized multicenter phase 3 clinical trial as induction and maintenance therapy for active CD (Clinical trial registry number NCT02685683 and NCT02641392) as well as an open-label phase 3 trial in CD (NCT02685683) and a multicenter phase 2 trial on UC (NCT02601300) with mongersen are in progress. 122 Recently, Aiolos, a member of the Ikaros family, has been found to promote Th17 differentiation by suppressing IL-2 production.…”

Section: Th17 and Treg Plasticity And Its Clinical Importancementioning

confidence: 99%

Plasticity of Th17 and Tregs and its clinical importance as therapeutic target in inflammatory bowel disease

Kulkarni¹,

Sonar²,

Lal³

2018

IJIR

View full text Add to dashboard Cite

The gut immune system is very complex and a single layer of the epithelial barrier along the gastrointestinal tract prevents the evasion of various extracellular commensal and pathogenic microorganisms in the gut mucosa. The inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD). The cause of IBD is thought to be associated with genetic, epigenetic, environmental factors, dietary habits and gut microbiota. Immunologically, the effector CD4 + T cells such as Th1, Th17, and regulatory CD + T cells play an important role in the pathogenesis of IBD. During gut inflammation and autoimmunity, these cells show phenotypic and functional plasticity, and differentiate into other lineages as well as have mixed-lineage phenotypes such as Th1-Th17, Th1-Treg, and Th17-Treg. The present review discusses the intrinsic and extrinsic factors that affect the cellular and molecular plasticity of Th17 and Treg, their clinical importance, and how plasticity and reprogramming of these cells can be targeted to control the IBD. Pathological features and distributionContinuous inflammation of the inner most epithelial layer of colon and the rectum and show superficial ulcers in the mucosa and submucosa. 178

show abstract

Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn’s disease

Cited by 38 publications

References 44 publications

Reverse plasticity: TGF‐β and IL‐6 induce Th1‐to‐Th17‐cell transdifferentiation in the gut

Reverse plasticity: TGF‐β and IL‐6 induce Th1‐to‐Th17‐cell transdifferentiation in the gut

Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7

Plasticity of Th17 and Tregs and its clinical importance as therapeutic target in inflammatory bowel disease

Contact Info

Product

Resources

About