Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm

Guo, Dong; Wang, Ye-Wei; Ma, Ji; Yan, Lei; Li, Teng-Fei; Han, Xinwei; Shui, Shaofeng

doi:10.1016/j.apjtm.2016.03.020

Cited by 11 publications

(10 citation statements)

References 19 publications

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“…Another important finding in the present study was that the ANXA3 silencing acted as an inhibitor of JNK expression, which led to the promotion of VSMC proliferation and reduced VSMC apoptosis. The proliferation and apoptosis of VSMCs were normally involved in maintaining the blood vessels, 13 the layer of which was frequently lacking in tumor vessels, promoting tumor invasion and metastasis 29 . Guo et al 13 .…”

Section: Discussionmentioning

confidence: 99%

“…As a family member of mitogen-activated protein kinase (MAPK), JNK was also correlated with IA, where JNK mainly undergoes cell proliferation, migration, differentiation, apoptosis, and inflammation 12 . Recent studies have demonstrated that excessive apoptosis of vascular smooth muscle cells (VSMCs) may be an important factor for the cerebral aneurysm formation, and the JNK pathway may be the pro-apoptotic pathway of VSMCs 13 . It has been found that ANXA3 promoted the tumor formation by JNK signaling pathway activation in the liver cancer stem cells 14 .…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway

Wang

Yang

et al. 2019

Molecular Therapy - Nucleic Acids

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Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), β-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway

Wang

Yang

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Statins inhibit Rho kinase activity in patients with atherosclerosis (Nohria et al., ). Moreover, a recent study showed that RhoA/ROCK signaling regulated smooth muscle phenotypic modulation and vascular remodeling (Tang et al., ) and the activation of JNK is important in the development of cerebral aneurysm (Guo et al., ). In the present study, LIG exerted an effect on suppressing AngII‐induced VSMCs migration.…”

Section: Discussionmentioning

confidence: 99%

Ligustilide Inhibited Rat Vascular Smooth Muscle Cells Migration via c‐Myc/MMP2 and ROCK/JNK Signaling Pathway

Luo

Deng

Fang

et al. 2019

Journal of Food Science

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Vascular smooth muscle cells (VSMCs) excessive migration, a basic change of pathological intimal thickening, can lead to serious cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke. Ligustilide (LIG), the main active ingredient of angelica volatile oil, has been demonstrated to exert protective effects on the cardiovascular and cerebrovascular, circulatory system, and immune function. However, whether it protects against intimal thickening and VSMCs excessive migration and its underlying mechanism remains largely unknown. The aim of this study is to investigate the effect of LIG on VSMCs migration and its underlying mechanism. The protective effect of LIG on VSMCs excessive migration was assessed using an atherosclerotic spontaneously hypertensive rat model and an angiotensin II (AngII)-induced VSMCs migration model. The results showed that LIG exerted a protective effect against pathological intimal thickening as demonstrated by decreasing VSMCs migration in vivo and in vitro. In vivo, intimal thickening and VSMCs migration were inhibited and LIG performed a suppressive effect on the expression of c-Myc protein while enhanced phenotypic transformation related proteins α-SMA expression. Meanwhile, the administration of LIG significantly lowered the blood pressure and blood lipids level in atherosclerotic spontaneously hypertensive rats. In vitro, LIG suppressed AngII-induced VSMCs migration and downregulated the expression of migration related protein c-Myc, MMP2, ROCK1, ROCK2, p-JNK, and JNK. These findings suggested the protective effect of LIG on VSMCs migration was associated with the decrement of c-Myc/MMP2 signaling pathway and ROCK-JNK signaling pathway. Thus, LIG may serve as a novel therapeutic agent for preventing cardiovascular disease.

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“…Notably, there is evidence that inhibiting inflammation in the aortic wall coupled with promoting VSMC proliferation has an essential component in the treatment an aneurysm rupture . Recent studies are acknowledged for their findings pertaining to the molecular pathogenesis of IAs that focus on VSMC activities …”

Section: Introductionmentioning

confidence: 99%

“…6 Recent studies are acknowledged for their findings pertaining to the molecular pathogenesis of IAs that focus on VSMC activities. 7,8 Serine-arginine protein-specific kinases (SRPKs) are pivotal regulators in transducing growth signals from the cell surface to the nucleus in order to regulate mRNA splicing. 9 The structure of SRPKs comprises a conserved kinase domain which is separated by a large, non-conserved insert domain approximately 250 amino acids in size.…”

Section: Introductionmentioning

confidence: 99%

SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms

Wang

2018

CNS Neurosci Ther

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Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm

Cited by 11 publications

References 19 publications

RETRACTED: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway

RETRACTED: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway

Ligustilide Inhibited Rat Vascular Smooth Muscle Cells Migration via c‐Myc/MMP2 and ROCK/JNK Signaling Pathway

SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms

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