• Journal of Ginseng Research
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• 제47권1호
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• pp.133-143
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• 2023

Background: Past studies suggested that ginseng extracts and ginseng-derived molecules exerted significant regulatory effects on skin. However, no reports have described the effects of ginseng-derived nanoparticles (GDNPs) on skin cell proliferation and wound healing. In this study, we investigated whether GDNPs regulate the proliferation of skin cells and promote wound healing in a mouse model. Methods: GDNPs were separated and purified via differential centrifugation and sucrose/D2O gradient ultracentrifugation. GDNP uptake, cell proliferation and cell cycle progression were measured by confocal microscopy, CCK-8 assay and flow cytometry, respectively. Cell migration and angiogenic effects were assessed by the wound scratch assay and tube formation assay, respectively. ELISA was used to detect extracellular matrix secretion. The relevant signaling pathway was confirmed by western blotting. The effects of GDNPs on skin wound healing were assessed by wound observation, HE staining, and western blotting. Results: GDNPs possessed the essential features of exosomes, and they were accumulated by skin cells. Treatment with GDNPs notably enhanced the proliferation of HaCaT, BJ and HUVECs. GDNPs also enhanced the migration in HaCaT cells and HUVECs and angiogenesis in HUVECs. GDNPs increased the secretion of MMP-1, fibronectin-1, elastin-1, and COL1A1 in all three cell lines. GDNPs regulated cell proliferation through the ERK and AKT/ mTOR pathways. Furthermore, GDNPs facilitated skin wound healing and decreased inflammation in a mouse skin wound model. Conclusion: GDNPs can promote skin wound healing through the ERK and AKT/mTOR pathways. GDNPs thus represent an alternative treatment for chronic skin wounds.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3757-3760
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• 2013

MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-485 mimics in breast carcinoma T47D cells. Forty-eight hours after T47D cells were transfected with miR-485 mimics, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects on cell viability. Colony formation and cell migration assays were adopted to determine whether miR-485 affects the proliferation rates and cell migration of breast carcinoma T47D cells. Our results showed that ectopic expression of miR-485 resulted in a significant decrease in cell growth, cell colony formation, and cell migration. These findings suggest that miR-485 might play an important role in breast cancer by suppressing cell proliferation and migration.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.182.2-182.2
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• 2003

The abnormal proliferation and migration of vascular smooth muscle cell (SMC) play an important role in the pathology of coronary artery atherosclerosis and restenosis. Platelet-derived growth factor (PDGF) is one of the most potent promoters of the proliferation and migration of the SMC. The heterocyclic quinones represent an important class of biologically active molecules. However, the inhibitory activity of quinone classes on the proliferation of the SMC has not been reported. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.223.2-224
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• 2003

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival and differentiation. GDNF increased proliferation and migration of Hs683 human giloma and C6 rat giloma cells in a dose-dependent manner. (omitted)

• Journal of Ginseng Research
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• 제40권4호
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• pp.325-333
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• 2016

Background: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng. LPA plays a key role in angiogenesis and wound healing. Methods: In the present study, we investigated the in vitro effects of gintonin on proliferation, migration, and tube formation of HUVECs, which express endogenous LPA1/3 receptors. Results: Gintonin stimulated proliferation and migration of HUVECs. The LPA1/3 receptor antagonist, Ki16425, short interfering RNA against LPA1 or LPA3 receptor, and the Rho kinase inhibitor, Y-27632, significantly decreased the gintonin-induced proliferation, migration, and tube formation of HUVECs, which indicates the involvement of LPA receptors and Rho kinase activation. Further, gintonin increased the release of vascular endothelial growth factors from HUVECs. The cyclooxygenase-2 inhibitor NS-398, nuclear factor kappa B inhibitor BAY11-7085, and c-Jun N-terminal kinase inhibitor SP600125 blocked the gintonin-induced migration, which shows the involvement of cyclooxygenase-2, nuclear factor kappa B, and c-Jun N-terminal kinase signaling. Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginsenginduced angiogenic and wound-healing effects.

• Journal of Acupuncture Research
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• 제24권5호
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• pp.23-32
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• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.

• 한국자원식물학회지
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• 제33권4호
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• pp.263-270
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• 2020

이상의 연구 결과로 미루어 볼 때, 댕댕이나무 잎과 가지 추추출물은 대장암 세포주 HCT116과 SW480세포의 생육을 억제하였으나 열매추출물은 억제활성이 나타나지 않았다. 잎과 가지 추출물은 cell migration과 wound healing assay를 통해 비정상적인 세포증식 억제를 확인하였으며, β-catenin과 TCF4의 단백질 수준을 감소시켜 비정상적인 Wnt 신호전달을 억제를 통해 대장암세포의 생육을 억제하는 것으로 판단된다. 따라서 댕댕이나무 잎과 가지는 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다.

• Molecules and Cells
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• 제20권3호
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• pp.429-434
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• 2005

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

• Molecules and Cells
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• 제39권4호
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• pp.345-351
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• 2016

Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.347-355
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• 2022

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.