Embelin inhibits abdominal aortic aneurysm through decreasing IL‑6‑induced STAT3 and NF‑κB inactivation

Liu, Qiang; Wang, Qingshan; Li, Haibin

doi:10.3892/mmr.2018.9221

Cited by 9 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metformin has been reported to inhibit the AngIIinduced AAA progression in mice through decreased the activity of NF-κB and STAT3 signal pathways 29 . Embelin inhibited AAA formation through decreasing IL-6 induced STAT3 and NF-κB inactivation 10 . All these studies indicate that targeting JAK2/STAT3 and NF-κB may be an effective strategy for AAA treatment.…”

Section: Discussionmentioning

confidence: 99%

“…For example, metformin has been reported to inhibit the angiotensin II (AngII) induced AAA progression in mice through decreased the activity of NF-κB and STAT3 signal pathway 8,9 . Embelin inhibits AAA formation through decreasing IL-6 induced STAT3 and NF-κB inactivation 10 . NF-κB is a family of transcriptional factors implicated in the processes of both inflammatory responses and oxidative stress which can promote chronic inflammation in the aortic wall, and regulate MMPs transcription 11 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Cheng

Zhao

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammationrelated signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE −/− mice were investigated. AAA was induced in ApoE −/− mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Cheng

Zhao

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Authors demonstrated that STAT3 signaling plays a crucial role in PK2 regulation and that phosphorylated STAT3 can directly bind to the Pk2 promoter. Furthermore, a recent study [29] demonstrated that phosphorylated STAT3 levels were significantly increased after BTZ administration and that STAT3 activation in DRG contributes to BIPN. On the basis of these data, we can speculate that the activation of STAT3, consequent to pro-inflammatory cytokine increase in the peripheral nervous stations [30], could be one of the mechanisms involved in the PK2 upregulation.…”

Section: Discussionmentioning

confidence: 99%

Targeting prokineticin system counteracts hypersensitivity, neuroinflammation, and tissue damage in a mouse model of bortezomib-induced peripheral neuropathy

Moschetti

Amodeo

Maftei

et al. 2019

J Neuroinflammation

View full text Add to dashboard Cite

Background Neuropathy is a dose-limiting side effect of many chemotherapeutics, including bortezomib. The mechanisms underlying this condition are not fully elucidated even if a contribution of neuroinflammation was suggested. Here, we investigated the role of a chemokine family, the prokineticins (PKs), in the development of bortezomib-induced peripheral neuropathy (BIPN), and we used a PK receptor antagonist to counteract the development and progression of the pathology. Methods Neuropathy was induced in male C57BL/6J mice by using a protocol capable to induce a detectable neuropathic phenotype limiting systemic side effects. The presence of allodynia (both mechanical and thermal) and thermal hyperalgesia was monitored over time. Mice were sacrificed at two different time points: 14 and 28 days after the first bortezomib (BTZ) injection. At these times, PK system activation (PK2 and PK-Rs), macrophage and glial activation markers, and cytokine production were evaluated in the main station involved in pain transmission (sciatic nerve, DRG, and spinal cord), and the effect of a PK receptors antagonist (PC1) on the same behavioral and biochemical parameters was assessed. Structural damage of DRG during BTZ treatment and an eventual protective effect of PC1 were also evaluated. Results BTZ induces in mice a dose-related allodynia and hyperalgesia and a progressive structural damage to the DRG. We observed a precocious increase of macrophage activation markers and unbalance of pro- and anti-inflammatory cytokines in sciatic nerve and DRG together with an upregulation of GFAP in the spinal cord. At higher BTZ cumulative dose PK2 and PK receptors are upregulated in the PNS and in the spinal cord. The therapeutic treatment with the PK-R antagonist PC1 counteracts the development of allodynia and hyperalgesia, ameliorates the structural damage in the PNS, decreases the levels of activated macrophage markers, and prevents full neuroimmune activation in the spinal cord. Conclusions PK system may be a strategical pharmacological target to counteract BTZ-induced peripheral neuropathy. Blocking PK2 activity reduces progressive BTZ toxicity in the DRG, reducing neuroinflammation and structural damage to DRG, and it may prevent spinal cord sensitization.

show abstract

“…Several reports stated that IL6 is a crucial gene involved in AAA development and pathogenesis. Liu et al (13) found that embelin can inhibit AAA through decreasing IL6-induced STAT3 and NF-κB inactivation. Nishihara et al (14) suggested that the level of IL6 in human AAA tissue may reflect the degree of other studies.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

Xie

Wang

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

show abstract

Embelin inhibits abdominal aortic aneurysm through decreasing IL‑6‑induced STAT3 and NF‑κB inactivation

Cited by 9 publications

References 41 publications

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Targeting prokineticin system counteracts hypersensitivity, neuroinflammation, and tissue damage in a mouse model of bortezomib-induced peripheral neuropathy

Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

Contact Info

Product

Resources

About