Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ

Zhang, Jiru; Lu, Qing-Bo; Feng, Wu-Bing; Wang, Huiping; Tang, Zihan; Cheng, Han Ping; Du, Qiong; Wang, Yuan-Ben; Li, Ke‐Xue; Sun, Hai-Jian

doi:10.1016/j.biopha.2018.03.120

Cited by 29 publications

(21 citation statements)

References 48 publications

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“…Peripheral nesfatin-1 exerts pronounced effects on the cardiovascular system, namely an increase in blood pressure after IP administration in mice [ 139 ] and rats [ 140 ] or IV injection in rats [ 141 ], with inhibited relaxation of peripheral blood vessels probably contributing to this effect [ 141 ]. This effect is likely associated with stimulated signaling of the phosphoinositide-3-kinase (PI3K)/AKT/ m -TOR pathway and phosphorylation of Janus kinase 2 (JAK2)/STAT3, resulting in proliferation, migration, and phenotype switch of vascular smooth muscle cells from a contractile to a synthetic state by elevating the mRNA and protein expression of matrix metalloproteinase 2 and 9 while reducing peroxisome proliferator-activated receptor-γ [ 142 , 143 ]. Because NUCB2 mRNA expression was increased in the media of the aorta of spontaneously hypertensive rats [ 142 ], nesfatin-1 might play a pathogenetic role under these conditions.…”

Section: Implications Of Nesfatin-1 In Cardiovascular Functionsmentioning

confidence: 99%

Current Understanding of the Role of Nesfatin-1

Schalla

Stengel

2018

Journal of the Endocrine Society

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Nesfatin-1 was discovered in 2006 and implicated in the regulation of food intake. Subsequently, its widespread central and peripheral distribution gave rise to additional effects. Indeed, a multitude of actions were described, including modulation of gastrointestinal functions, glucose and lipid metabolism, thermogenesis, mediation of anxiety and depression, as well as cardiovascular and reproductive functions. Recent years have witnessed a great increase in our knowledge of these effects and their underlying mechanisms, which will be discussed in the present review. Lastly, gaps in knowledge will be highlighted to foster further studies.

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Section: Implications Of Nesfatin-1 In Cardiovascular Functionsmentioning

confidence: 99%

Current Understanding of the Role of Nesfatin-1

Schalla

Stengel

2018

Journal of the Endocrine Society

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“…TIMPs plays a central role in suppressing the activation of MMPs. TIMPs-MMPs have been identi ed as the key molecular in vascular remodeling and are linked to VSMCs proliferation and migration [30][31][32][33]. SM22α is a contractile marker of VSMCs, it affects the proliferation of VSMCs and the development of AS [5].…”

Section: Discussionmentioning

confidence: 99%

The Compatibility of Alisma and Atractylodes Affects the Biological Behaviors of VSMCs Via Inhibiting miR-128-5p / p21 Gene

Wei

Shen

et al. 2020

Preprint

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Background：The compatibility of Alisma and Atractylodes (AA) has been estimated to exhibit anti-atherosclerotic effects, while the mechanism still remains unclear. This study was aimed to identify the role of AA on oxidized low density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) behaviors, and to explore the effect of microRNAs (miRNAs). Methods：Scratch wound healing assay detected the migration of VSMCs, immunocytochemistry assay and western blot of SM22ɑ were used to evaluated the phenotypic transformation. Bromodeoxyuridine (Brdu) immunocytochemistry and flow cytometry were applied to detect the proliferation of VSMCs. The miRNA microarray profiling was performed using lianchuan biological small RNA sequencing analysis. VSMCs were transfected with the miR-128-5p mimic and inhibitor, the migration, phenotypic modulation and proliferation of VSMCs were investigated. The 3'UTR binding sequences site of miR-128-5p on p21 gene were predicted and assessed by luciferase assays.Results：AA and extracellular regulated protein kinases 1/2 (ERK1/2) blocker U0126 markedly inhibited the ability of migration, elevated smooth muscle 22alpha (SM22α) expression, repressed VSMCs proliferation, elevated the expression of miR-466f-3p and miR-425-3p, while suppressed miR-27a-5p and miR-128-5p expression in the ox-LDL-induced VSMCs. MiR-128-5p targets tissue inhibitor of metalloproteinase (TIMPs), silent information regulator 2 (SIRT2), peroxisome proliferator-activated receptors (PPARs) and p21 genes, which is linked to the behaviors of VSMCs. MiR-128-5p mimic promoted migration and proliferation of VSMCs, and suppressed the p21, p27 and SM22ɑ expression. The inhibitor increased p21, p27 and SM22ɑ expression, and repressed the migration, phenotypic transformation and proliferation of VSMCs. MiR-128-5p directly targeted the 3′UTR binding sequences of p21 gene, negatively regulated p21 expression and exerted a role in the proliferation of VSMCs.Conclusion：Our research showed that the migration, phenotypic transformation and proliferation of ox-LDL-induced VSMCs were repressed by AA through inhibiting miR-128-5p via targeting p21 gene, which may provide an effective option for the treatment of Atherosclerosis.

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“…33) MMP-9, a pivotal member of MMPs, plays an important role in cell growth, migration and angiogenesis. 34,35) Previous reports have showed that MMP-9 promoted neointima formation in animal models. 36,37) Huang et al found that Cantharidin can exert an anti-metastasis effect by inhibiting MMP-9 in TSGH-8301 human bladder cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…34,35) Previous reports have showed that MMP-9 promoted neointima formation in animal models. 36,37) Huang et al found that Cantharidin can exert an anti-metastasis effect by inhibiting MMP-9 in TSGH-8301 human bladder cancer cells. 38) Similarly, our results (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response

Qiu

Jiang

et al. 2019

Biological & Pharmaceutical Bulletin

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Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the chronic inflammation regulated by various inflammatory factors are the major pathological processes in the development of neointimal hyperplasia and in-stent restenosis after angioplasty. Cantharidin is a potent and selective inhibitor of protein phosphatase 2A, which plays pivotal roles in cell cycle progression, cell fate, and inflammation. This study was to explore whether Cantharidin could inhibit VSMCs proliferation, migration and inflammation. Transwell migration assay, Cell Counting Kit 8 and flow cytometry were performed. Western blot, Quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of the markers. Results showed that Cantharidin remarkably suppressed VSMCs proliferation and migration induced by platelet derived growth factor (PDGF)-BB. Meanwhile, Cantharidin could significantly inhibit the phosphorylation of Akt (P-AKT) and p38 mitogen-activated protein kinase (MAPK) (P-p38), the expression of p38 MAPK (p38), and also the phosphorylation level of nuclear factor-kappaB (NF-κB) p65 (p65). Cantharidin obviously inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and also the level of IL-6 and TNF-α in culture supernatants. Inhibitors for p38 MAPK, phosphatidylinositol 3-kinase (PI3K) /AKT and NF-κB signaling pathways did not affect the inhibition of Cantharidin on VSMCs proliferation, migration and inflammation. These findings indicated that Cantharidin could significantly inhibit the proliferation, migration and inflammatory response of VSMCs, which suggested that Cantharidin may be a potential inhibitor for neointimal hyperplasia and restenosis after angioplasty.

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Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ

Cited by 29 publications

References 48 publications

Current Understanding of the Role of Nesfatin-1

Current Understanding of the Role of Nesfatin-1

The Compatibility of Alisma and Atractylodes Affects the Biological Behaviors of VSMCs Via Inhibiting miR-128-5p / p21 Gene

Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response

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