PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease

Ibrahim, Sidikjan; Zhu, Xu; Luo, Xuelai; Feng, Yongdong; Wang, Jing

doi:10.1016/j.intimp.2020.106610

Cited by 48 publications

(34 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[13] Meanwhile, the substantial inflammatory cytokines can further facilitate the progression of IBD, leading to disruption of mucosal barrier damage and loss of tight junction protein (ZO-1). [14] The M1 polarization is regulated by ROS. In the early stage of polarization, macrophages express ROS substantially.…”

Section: Discussionmentioning

confidence: 99%

Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization

Ruan

Zha

2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

This study focuses on exploring the role and mechanism of moronic acid (MOA), a small triterpenoid molecule, against inflammatory bowel disease (IBD). Intestinal macrophages were cultured in vitro, and their M1 polarization was induced by lipopolysaccharide (LPS) and interferon gamma (IFN‐γ). After intervention with MOA, the proportion of M1 macrophages was detected, and the levels of inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β) were examined by ELISA. IFA staining was performed to determine the P50 and CD86 expressions, while DCFH‐DA was used to determine the reactive oxygen species (ROS) level, as well as the p‐P50 and NLRP3 protein levels. Additionally, we also used N‐acetylcysteine, a ROS inhibitor, to further explore the association between MOA and ROS‐NF‐κB signaling. In murine experimentation, colitis was induced in mice with DSS. After MOA intervention, we assessed the mucosal barrier damage, tissue ROS, as well as protein and inflammatory cytokine levels. MOA could inhibit the M1 polarization of intestinal macrophages, suppress the expressions of inflammatory cytokines, and reduce the level of ROS‐NF‐κB‐NLRP3 signaling. After inhibiting ROS through NAC treatment, the effect of MOA was evidently weakened. Clearly, MOA exerted its activity via ROS. In the murine model, MOA could lower the CD86 level in the intestinal tissues, inhibit the M1 polarization of macrophages, and reduce the tissue levels of inflammatory cytokines. This study finds that MOA can regulate ROS‐NF‐κB‐NLRP3 signaling by inhibiting ROS, thereby suppressing the M1 polarization of intestinal macrophages, which plays a protective role in IBD.

show abstract

Section: Discussionmentioning

confidence: 99%

Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization

Ruan

Zha

2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…In addition, IAP ameliorated lipopolysaccharide (LPS)-induced inflammation and relocation of ZO-1 at TJ improving epithelial barrier integrity[ 68 ]. Furthermore, Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) inhibited the expression of ZO-1 in Caco-2 cells and decreased TJ barrier permeability which was improved after PIK3R3 inhibitor TAT-N 15[ 69 ]. Transcription factor JunD repressed ZO-1 expression through cAMP response element-binding protein-binding (CREB) in colon cancer Caco-2 cells impairing intestinal barrier integrity[ 30 ].…”

Section: Expression Of Zo Proteins In Colon Cancermentioning

confidence: 99%

Role of zonula occludens in gastrointestinal and liver cancers

Ram¹,

Vairappan²

2022

WJCC

View full text Add to dashboard Cite

A growing body of evidence suggests that tight junction (TJ) proteins play a crucial role in the pathogenesis of various diseases, including gastrointestinal (GI) cancer and hepatocellular carcinoma (HCC). TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however, recent reports suggest that they also regulate gene expression necessary for cell proliferation, angiogenesis, and metastasis through adapter proteins such as zonula occludens (ZO). ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors. Reduced ZO proteins in GI cancer and HCC are correlated with tumor development and poor prognosis. Pubmed has searched for using the keyword ZO and gastric cancer, ZO and cancer, and ZO and HCC for the last ten years to date. This review summarized the role of ZO proteins in cell proliferation and their expression in GI cancer and HCC. Furthermore, therapeutic interventions targeting ZO in GI and liver cancers are reviewed.

show abstract

“…Inflammatory bowel disease (IBD) is non-specific colitis, mainly including ulcerative colitis (UC) and Crohn’s disease (CD), with symptoms such as abdominal pain, diarrhea, and weight loss [ 1 ]. Currently, the prevalence of IBD is on the rise worldwide, with a prevalence of 10–20% in developed countries and more severe in developing countries [ 2 , 3 ]. Pharmacological treatment of IBD in modern society mainly uses drugs such as 5-aminosalicylates and immunosuppressive agents.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory bowel disease: an overview of Chinese herbal medicine formula-based treatment

Yuan

Wang

et al. 2022

Chin Med

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the intestine, including Crohn’s disease (CD) and ulcerative colitis (UC), whose etiology and pathogenesis have not been fully understood. Due to its prolonged course and chronic recurrence, IBD imposes a heavy economic burden and psychological stress on patients. Traditional Chinese Herbal Medicine has unique advantages in IBD treatment because of its symptomatic treatment. However, the advantages of the Chinese Herbal Medicine Formula (CHMF) have rarely been discussed. In recent years, many scholars have conducted fundamental studies on CHMF to delay IBD from different perspectives and found that CHMF may help maintain intestinal integrity, reduce inflammation, and decrease oxidative stress, thus playing a positive role in the treatment of IBD. Therefore, this review focuses on the mechanisms associated with CHMF in IBD treatment. CHMF has apparent advantages. In addition to the exact composition and controlled quality of modern drugs, it also has multi-component and multi-target synergistic effects. CHMF has good prospects in the treatment of IBD, but its multi-agent composition and wide range of targets exacerbate the difficulty of studying its treatment of IBD. Future research on CHMF-related mechanisms is needed to achieve better efficacy.

show abstract

PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease

Cited by 48 publications

References 27 publications

Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization

Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization

Role of zonula occludens in gastrointestinal and liver cancers

Inflammatory bowel disease: an overview of Chinese herbal medicine formula-based treatment

Contact Info

Product

Resources

About