RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton

Tang, Lian; Dai, Fan; Liu, Yan; Yu, Xiaoqiang; Huang, Chao; Wang, Xueying; Yao, Wenjuan

doi:10.1016/j.phrs.2018.05.011

Cited by 77 publications

(62 citation statements)

References 29 publications

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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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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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“…However, unexpectedly, the phosphorylation of p38MAPK, ERK1/2, and AKT by PDGF remained unaltered in the stimulation of carnosine. The role and importance of JNK signaling has been identified in PDGF-induced VSMC proliferation both in the in vitro and in vivo models [26,27]. Inhibition of JNK signaling has been suggested to be one of the main targets to consider while developing agents for the treatment of vascular diseases [26,27].…”

Section: Discussionmentioning

confidence: 99%

Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo

et al. 2020

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Carnosine, a naturally producing dipeptide, exhibits various beneficial effects. However, the possible role of carnosine in vascular disorders associated with pathological conditions, including proliferation and migration of vascular smooth muscle cells (VSMCs), largely remains unrevealed. Here, we investigated the regulatory role and mechanism of carnosine in platelet-derived growth factor (PDGF)-induced VSMCs. Carnosine inhibited the proliferation of PDGF-induced VSMCs without any cytotoxic effects. Carnosine treatment also induced G1-phase cell cycle arrest by causing a p21WAF1-mediated reduction in the expression of both cyclin-dependent kinases (CDKs) and cyclins in PDGF-treated VSMCs. Carnosine treatment suppressed c-Jun N-terminal kinase (JNK) phosphorylation in PDGF-stimulated signaling. Additionally, carnosine significantly prevented the migration of VSMCs exposed to PDGF. Carnosine abolished matrix metalloproteinase (MMP)-9 activity via reduced transcriptional binding activity of NF-κB, Sp-1, and AP-1 motifs in PDGF-treated VSMCs. Moreover, using aortic assay ex vivo, it was observed that carnosine addition attenuated PDGF-stimulated sprout outgrowth of VSMCs. Taken together, these results demonstrated that carnosine impeded the proliferation and migration of PDGF-stimulated VSMCs by regulating cell cycle machinery, JNK signaling, and transcription factor-mediated MMP-9 activity as well as prevented ex vivo sprout outgrowth of blood vessels. Thus, carnosine may be a potential candidate for preventing vascular proliferative disease.

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“…Concurrently, Cbx3 and Lyn which serve as proliferation promotional regulators were slightly downregulated and upregulated, respectively (Figure 5c iii-iv). ROCK signaling pathway plays a crucial role in actin cytoskeleton rearrangement and mediates various cellular manners, including cell morphology, adhesion, proliferation, migration, and contractility 34 . Through immunofluorescence staining, we observed significantly more elongated vSMCs when cultured on VWMFs, showing an average cellular aspect ratio of 5.0±2.34 vs. 1.84±0.73, respectively (Supplementary Figure 16).…”

Section: D Culturing Inducing Highly Physiologically Relevant Phenotmentioning

confidence: 99%

Inducing highly physiologically relevant phenotypes of human vascular smooth muscle cells via 3D printing

Zhu

Wang

et al. 2020

Preprint

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Vascular smooth muscle cells (vSMCs) are one of the essential cell types in blood vessel walls. A significant vSMC phenotype characteristic is that they collectively wrap around the outer layer of the healthy blood vessels with spindle-like morphology and help maintain the vascular tones and regulate the blood flow. Both physiological and biomedical research are impeded by the standard 2D cell culture approaches which do not create in vivo like microenvironment. Here, we systematically investigated the vSMCs culturing within 3D printed geometrical constraints and on printed microfilaments. Based on these models, we demonstrate a simple bioprinting approach for fast manufacturing vessel architectures with micro-grooved surfaces for vSMCs alignment. We validated that the vSMCs cultured on the printed vessel with microfilaments (VWMF) present a more physiologically relevant morphological phenotype and gene expression profile, and they are considerably more active in wound healing and ischemia than conventional planarly cultured vSMCs.

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RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton

Cited by 77 publications

References 29 publications

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

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

Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo

Inducing highly physiologically relevant phenotypes of human vascular smooth muscle cells via 3D printing

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