Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice

As a noted medicinal mushroom, Ganoderma lucidum (G. lucidum) has been reported to have a number of pharmacological effects such as anti-tumor and liver protection. Compared with the common ethanol reflux method, supercritical CO2 extraction has obvious advantages in obtaining antitumor extracts from G. lucidum fruiting body such as short extraction time, low temperature and no solvent residue. However, Using high-pressure supercritical CO2 without entrainer to obtain the antitumor extracts from G. lucidum and studying their anti-hepatoma effect have not been reported. In this study, high-pressure supercritical CO2 extracts obtained under 65, 85, and 105 MPa pressure named as G65, G85, G105 respectively and ethanol reflux extract (GLE) were used to investigate their anti-hepatoma activity and the underlying molecular mechanism. The total triterpenoid content of G85 was significantly higher than that of G65 and GLE, but did not differ significantly from that of G105 by UV and high-performance liquid chromatography. GLE, G65, and G85 could inhibit cell proliferation, arrest cell cycle in G2/M phase, and induce apoptosis in two liver cancer cell lines (QGY7703 and SK-Hep1), of which G85 had the strongest effect. The results showed that the potency of their cytotoxicity of the high-pressure supercritical CO2 extracts on human hepatoma carcinoma cells in vitro was consistent with their total triterpenoid content. G85 exhibited significant anti-hepatoma effect with low toxicity In vivo. Further mechanistic investigation revealed that the anti-tumor effect of these extracts was associated with their inhibition of Ras/Raf/MEK/ERK signaling pathway. Our findings suggest that the high-pressure supercritical CO2 extraction of G. lucidum fruiting body can be used to obtain a triterpenoid-rich anti-tumor agent, which may have potential clinical significance for the treatment of human hepatoma.

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CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway

Journal of Surgical Research ◽

10.1016/j.jss.2013.05.065 ◽

2013 ◽

Vol 185 (2) ◽

pp. e109-e119 ◽

Cited By ~ 10

Author(s):

Elizabeth Kiwanuka ◽

Florian Hackl ◽

Edward J. Caterson ◽

Daniel Nowinski ◽

Johan P.E. Junker ◽

...

Keyword(s):

Signaling Pathway ◽

Erk Signaling ◽

Keratinocyte Migration

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Scutellarin Attenuates Human-Neutrophil-Elastase-Induced Mucus Production by Inhibiting the PKC-ERK Signaling Pathway in Vitro and in Vivo

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009494 ◽

2011 ◽

Vol 39 (06) ◽

pp. 1193-1206 ◽

Cited By ~ 10

Author(s):

De-Peng Jiang ◽

Qi Li ◽

Jie Yang ◽

Juliy M. Perelman ◽

Victor P. Kolosov ◽

...

Keyword(s):

Signaling Pathway ◽

Neutrophil Elastase ◽

Human Neutrophil ◽

Erk Signaling ◽

Control Group ◽

Human Neutrophil Elastase ◽

Dependent Manner ◽

Mucus Production

The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 μM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal-regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease.

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Telocytes Promote the Metastasis of Hepatocellular Carcinoma by Activating ERK Signaling Pathway and Sponging miR-942-3p to Impact MMP9

10.21203/rs.3.rs-364558/v1 ◽

2021 ◽

Author(s):

Ying Xu ◽

Hu Tian ◽

Chao Guang Luan ◽

Kai Sun ◽

peng Jin Bao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Signaling Pathway ◽

Erk Signaling ◽

Cancer Tissue ◽

Proliferative Potential ◽

Cancer Tissues ◽

Hcc Cells

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.

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Schisantherin A Inhibits Pulmonary Fibrosis via Regulating ERK Signaling Pathway

Natural Product Communications ◽

10.1177/1934578x20948359 ◽

2020 ◽

Vol 15 (8) ◽

pp. 1934578X2094835

Author(s):

Wenyue Zhuang ◽

Na Zhao ◽

Di Li ◽

Xiaoming Su ◽

Yueyang Wang ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Western Blot ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Erk Signaling ◽

Mesenchymal Transition ◽

Tgf Β1 ◽

Schisantherin A

There is no effective method for treating pulmonary fibrosis (PF) until now. This study investigated the anti-fibrotic effect of schisantherin A (SCA) extracted from Schisandra chinensis and its potential molecular mechanism in PF. A bleomycin-induced PF mouse model in vivo and transforming growth factor (TGF)-β1-induced A549 epithelial-mesenchymal transition (EMT) cell model in vitro were used for assessing the anti-fibrotic effect of SCA. Histopathological examination was conducted after hematoxylin and eosin and Masson staining. The level of TGF-β1 was tested by ELISA. The expression levels of α-smooth muscle actin, E-cadherin, and inflammatory cytokines (COX2, IL-1β, IL-6, and TNF-α) were determined by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of extracellular signal-regulated kinase (ERK) was tested in lung tissues and cells by Western blot. The in vivo experiments revealed that SCA treatment markedly improved body weight and pulmonary index and reformed the destruction of the lung tissue structure. We observed that SCA inhibited the process of TGF-β1-induced EMT in the in vitro experiments. Inflammatory cytokines were reduced greatly in lung tissues and cells by SCA. Our study also indicated that SCA decreased phosphorylated ERK. It was concluded that SCA can attenuate PF by regulating the ERK signaling pathway, which suggests that SCA may be used as a potential therapeutic drug for PF.

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Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway

PLoS ONE ◽

10.1371/journal.pone.0134662 ◽

2015 ◽

Vol 10 (8) ◽

pp. e0134662 ◽

Cited By ~ 33

Author(s):

Fei Wu ◽

Haibo Song ◽

Yuan Zhang ◽

Yuzhu Zhang ◽

Qian Mu ◽

...

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

Umbilical Vein ◽

Erk Signaling ◽

Zebrafish Embryos ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

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Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

Cell & Bioscience ◽

10.1186/s13578-019-0348-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Yi Wang ◽

Zhiheng Guo ◽

Yongmei Gao ◽

Ping Liang ◽

Yanhong Shan ◽

...

Keyword(s):

Survival Rate ◽

Cardiac Hypertrophy ◽

Signaling Pathway ◽

Cardiac Remodeling ◽

Cardiac Fibrosis ◽

Cardiac Injury ◽

Erk Signaling ◽

Ang Ii ◽

Total Survival

Abstract Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.

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