Journal of Cancer Research and Therapeutics
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2020
·Vol. 16
·期 2
·209
·
IF 1.326
Yu Haipeng,Zhu Bolan,Yang Wan,Zhang Qian,Wang Wei,Zhai Weichun,Lu Lixia,Zheng Ying,Dang Zheng,Li Bin,Li Chuyi,Liang Bin,Zhang Jiucong,Yu Xiaohui
Objective: To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Methods: HepG2 cell was selected and divided into blank control group, experimental group ( matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. Results: With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). Conclusion: Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
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2025
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IF 4.3
Fan Yanan,An Caizhelin,Wang Zhihui,Luo Jia,Wang Wenbin,Luo Qing,Song Guanbin
Hepatocytes are the primary functional cells in the liver, and the malignant transformation of hepatocytes significantly contributes to hepatocellular carcinoma (HCC) progression. Liver fibrosis and cirrhosis caused by extracellular matrix (ECM) remodeling during liver lesions is a pivotal driver of HCC. However, the impact of matrix stiffness on hepatocytes and the underlying molecular mechanisms are not fully understood. Herein, using gelatin/sodium alginate hydrogels with different stiffnesses to simulate the change of matrix stiffness during liver lesions, we found that matrix stiffening leads to a notable decrease in the expression of hepatocyte nuclear factor 4α (HNF4α) and functional hepatocyte genes and a significant increase in the expression of interleukin 6 (IL‒6) in human hepatocyte line L‒02 cells, indicating obvious damage of hepatocyte function. In addition, matrix stiffening causes extensive DNA damage to L‒02 cells. Mechanistically, matrix stiffening upregulates piezo‒type mechanosensitive ion channel component 1 (Piezo1) expression and activates extracellular signal‒regulated kinase 1/2 (ERK1/2) signaling. Piezo1 knockdown suppresses matrix stiffening‒induced functional impairment and DNA damage in L‒02 cells. Moreover, Piezo1 knockdown blocks matrix stiffening‒activated ERK1/2 signaling in L‒02 cells. U0126 (a selective inhibitor of ERK1/2 activation) treatment could rescue matrix stiffening‒induced functional impairment and DNA damage. Taken together, these findings demonstrate that matrix stiffening induces functional impairment and DNA damage in L‒02 cells via the Piezo1‒ERK1/2 signaling pathway, which provides evidence for a better understanding of the hepatocyte function damage caused by tissue mechanical microenvironment change in liver diseases and the mechanotransduction in this process. Graphical abstract An increase in matrix stiffness inhibits HNF4α expression and promotes IL‒6 expression in L‒02 cells. Meanwhile, matrix stiffening induces L‒02 cell DNA damage and upregulates the expression of γ‒H2AX and 53BP1. These findings prove that matrix stiffness is a crucial mechanical regulator of cellular functional impairment and DNA damage and plays an important role in liver disease.
研究领域:
医学
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细胞生物学
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PubMed
高影响因子
NEUROTOXICOLOGY AND TERATOLOGY
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2025
·
IF 2.8
Fangfei Li,Jie Zhang,Xiaoli Ma,Hao Chen,Guiqiang Liang,Yunfeng Zou
Excessive accumulation of manganese (Mn) can cause neuroinflammation, impairing cognitive function. SPON1, a secreted glycoprotein in the extracellular matrix, is implicated in neuroinflammation, but its role in activating pro-inflammatory pathways in Mn-induced neuroinflammation remains unclear. This study employed in vivo and in vitro models to investigate Mn neuroinflammation. The expression levels of SPON1 and the ERK1/2/NF-κB pathway associated with inflammation were measured in male C57BL/6 mice after gavage of Mn at different doses (0, 25, 50, 100 mg/kg) for 12 weeks. SPON1 levels were measured after primary hippocampal neurons, primary cortical neurons, neuroblastoma cells (N2a), and microglial cells (BV2) were exposed to various concentrations of Mn for 24 h. We observed that in vivo Mn exposure significantly decreased SPON1 expression in the cortex but not in the hippocampus. Similarly, in vitro experiments demonstrated that Mn exposure significantly reduced SPON1 levels in primary cortical neurons, N2a, and BV2. In addition, Mn exposure increased the expression levels of ERK1/2 and NF-κB pathway proteins in the mouse cortex. Because BV2 cells are susceptible to inflammatory signals, they were chosen to elucidate how SPON1 induces neuroinflammation during Mn exposure. SPON1 knockdown increases the expression of inflammatory factors, whereas SPON1 overexpression inhibits the activation of the ERK1/2/NF-κB pathway and reduces inflammatory factor levels. In summary, these results suggest that Mn may affect the activation of ERK1/2/NF-κB pathway and the expression of inflammatory factors by inhibiting SPON1, ultimately promoting neuroinflammation.
研究领域:
神经科学
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毒理学
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分子生物学
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免疫学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2018
·Vol. 120
·期 5
·7602-7611
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IF 2.959
Xiaolin Wang,Teng Ma,Xiaojian Wan,Yan Meng,Zhenzhen Zhao,Jinjun Bian,Rui Bao,Xiaoming Deng,Tao Yang
IGFBP7 as an early biomarker has been used to identify patients at risk of developing acute kidney injury (AKI). Nevertheless, its role in AKI remains obscure. The aim of our study is to determine the role and mechanism of IGFBP7 in lipopolysaccharide (LPS)-induced HK-2 cells in vitro and on sepsis-induced AKI by cecal ligation and puncture (CLP) in vivo. Here, we identified that IGFBP7 expression was increased in patients with AKI and HK-2 cells with LPS (1, 2, and 5 μg/mL) induction. HK-2 cells with LPS induction showed cell cycle arrest at G1-G0 phases and cell apoptosis and activated ERK1/2 parallel with the changes in the proteins belonging to the ERK1/2 pathway, including Cyclin D1, P21, Bax, and Bcl-2, which were inhibited by the IGFBP7 knockdown. Moreover, IGFBP7 overexpression significantly induced cell cycle arrest at G1-G0 phases and cell apoptosis of HK-2 cells, which were inhibited by PD98509, an ERK1/2 signaling inhibitor. IGFBP7 knockdown effectively alleviated the severity of the renal injury, evidenced by decreases in the urinary levels of creatinine, blood urea nitrogen, and albumin, cell apoptosis, and activation of ERK1/2 signaling in CLP mice. Taken together, our findings indicate that IGFBP7 regulates sepsis-induced AKI through ERK1/2 signaling.
研究领域:
肾病学
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分子生物学
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细胞生物学
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传染病学
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PubMed
高影响因子
LIPIDS
·
2022
·Vol. 57
·期 3
·153-162
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IF 1.646
Danping Wang,Jinglong Chen,Huangbing Sun,Wenjing Chen,Xiaojing Yang
Oxidative stress is an important factor in the occurrence and development of liver disease. Medium-chain fatty acids (MCFAs) have potential antioxidant function, whereas the exact underlying mechanism of MCFA in oxidative injury of hepatocytes remains unclear. In our present study, three different MCFAs, 8-carbon octanoic acid (OA), 10-carbon capric acid (CA), and 12-carbon lauric acid (LA), have been performed to observe their protective action for hepatocyte under the H 2 O 2 challenge. The result showed that MCFA treatment significantly increased the cell viability, T-AOC, and expression of antioxidant-related genes in AML12 cells under oxidative stress condition, and reduced reactive oxygen species (ROS) production. Moreover, MCFA treatment significantly increased the protein expression of Nrf2 and the phosphorylation level of ERK1/2; LA treatment significantly promoted the Nrf2 nuclear translocation. With a further test, the rescue ability of MCFA was blocked by treating with the ERK inhibitor U0126. Overall, our data suggested that MCFA treatment has positive impact on protecting AML12 cells against oxidative stress through ERK1/2/Nrf2 pathway.
研究领域:
细胞生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2021
·
IF 6.684
Wang Jing,Zhang Yuan-wei,Zhang Nian-jie,Yin Shuo,Ruan Du-ji,He Nian,Chen Xu,Yang Xue-feng
Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.
研究领域:
肿瘤学
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分子生物学
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环境健康
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2020
·Vol. 22
·期 2
·774-782
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IF 2.1
Shiqiang Zhang,Yun Yang,Yunwei Hua,Chen Hu,Yi Zhong
Colorectal cancer is a digestive tract malignancy and the third leading cause of cancer‑related mortality worldwide. Norcantharidin (NCTD), the demethylated form of cantharidin, has been reported to possess anticancer properties. Family‑with‑sequence‑similarity‑46c (Fam46c), a non‑canonical poly(A) polymerase, has been reported to be critical in NCTD‑mediated effects in numerous types of cancer, including hepatoma. In the current study, it was found that Fam46c expression was reduced in colorectal cancer tissues and cells. Treatment with NCTD was observed to significantly enhance apoptosis and inhibit glycolysis in colorectal cancer cells. In addition, Fam46c and cleaved caspase 3 expression levels were found to be increased in response to NCTD treatment, in contrast to tumor‑specific pyruvate kinase M2 and phosphorylated ERK expression, which was reduced. Importantly, overexpression of Fam46c exerted similar effects as NCTD treatment on the apoptosis and glycolysis of colorectal cancer cells, whereas Fam46c knockdown strongly attenuated the effect of NCTD. Moreover, epidermal growth factor, which acts as an agonist of ERK1/2 signaling, weakened the effects of NCTD on colorectal cancer cells. Taken together, the results indicated that NCTD promotes apoptosis and suppresses glycolysis in colorectal cancer cells by possibly targeting Fam46c and inhibiting ERK1/2 signaling, hence suggesting that Fam46c may act as a tumor suppressor in colorectal cancer. Thus, the present study identified a novel therapeutic target of NCTD in the clinical treatment of colorectal cancer.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2023
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IF 3.1
Qiuxia Zhu,Yong Luo,Yuetao Wen,Ding Wang,Jing Li,Zhongcai Fan
Apoptosis is a major pathophysiological change following myocardial ischemia/reperfusion (I/R) injury. Glucagon-like peptide 1 (GLP-1) and its receptor GLP-1R are widely expressed in the cardiovascular system and GLP-1/GLP-1R activates the protein kinase G (PKG)-related signaling pathway. Therefore, this study tested whether semaglutide, a new GLP-1 analog, inhibits I/R injury-induced cardiomyocyte apoptosis by activating the PKG/PKCε/ERK1/2 pathway. We induced myocardial I/R injury in rats and hypoxia/reoxygenation (H/R) injury in H9C2 cells and detected the effects of semaglutide, a PKG analog (8-Br-cGMP), and a PKG inhibitor (KT-5823) on the PKG/PKCε/ERK1/2 pathway and cardiomyocyte apoptosis. We found that semaglutide upregulated GLP-1R levels, and both semaglutide and 8-Br-cGMP activated the PKG/PKCε/ERK1/2 pathway, inhibited myocardial infarction (MI), decreased hs-cTNT levels, increased NT-proBNP levels, and suppressed cardiomyocyte apoptosis in I/R rats and H/R H9C2 cells. However, KT-5823 exerted contrasting effects with semaglutide and 8-Br-cGMP, and KT-5823 weakened the cardioprotective effects of semaglutide. In conclusion, semaglutide inhibits I/R injury-induced cardiomyocyte apoptosis by activating the PKG/PKCε/ERK1/2 pathway. The beneficial effect of GLP-1/GLP-1R, involved in the activation of the PKG/PKCε/ERK1/2 pathway, may provide a novel treatment method for myocardial I/R injury.
研究领域:
心脏病学
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药理学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
·Vol. 76
·期 1
·109304
·
IF 3.7
Zhaoxia Yu,Shihui Jiang,Xinxin Li,Xingjiao Li,Guanhua Wang,Xiaohua Dai,Xiaoli Lian,Yan Yan,Yue Wang,Zhimou Yang,Huiru Zou
Objectives Enamel matrix derivative (EMD) is widely recognized for its ability to induce osteogenic and odontogenic differentiation. However, the complex composition of EMD frequently results to inconsistent experimental and clinical outcomes. Amelogenin, a key component of EMD, plays crucial roles in tooth germ development as well as in the repair and regeneration of dental tissue. In this study, an amelogenin peptide was investigated on the proliferation and odontogenic differentiation of human dental pulp cells (HDPCs). Methods The amelogenin peptide with the amino acid sequence KWYQNMIR was synthesized using solid-phase techniques. HDPCs were stimulated with various concentrations of the peptide. CCK-8 assays, alkaline phosphatase (ALP) activity measurements, quantitative reverse transcription-polymerase chain reaction, Western blot analysis, Alizarin red staining, and scanning electron microscopy were used to assess the effects. Results The amelogenin peptide concentrations of 100 nM and 1 μM significantly enhanced HDPC proliferation at 5 and 7 days ( P < .01), with 1 μM exhibiting the most pronounced effect. Treatment with 1 μM amelogenin peptide enhanced ALP activity in HDPCs at 7 and 14 days ( P < .01) and markedly upregulated the mRNA expression of DSPP, DMP-1 , and RUNX-2 . Western blot analysis revealed that 1 μM amelogenin peptide enhanced the protein expression of DSPP, DMP-1, and ALP in HDPCs at 7 and 14 days. Additionally, it promoted calcium deposition and mineralized nodule formation at 28 days. Importantly, the amelogenin peptide upregulated the phosphorylation level of ERK1/2 (p-ERK1/2), and the application of an ERK1/2 inhibitor suppressed HDPC differentiation. Conclusions The amelogenin peptide stimulates both the proliferation and odontogenic differentiation of HDPCs via the ERK1/2 pathway. These findings suggest that the amelogenin peptide may have significant implications for regenerative dentistry, particularly in the context of dentine-pulp complex regeneration.
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PubMed
高影响因子
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
·
2020
·Vol. 106
·期 2
·526-538
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IF 5.399
Wu Ying-Ting,Ma Si-Yu,Sun Wen-Qin,Shen Wei-Wei,Zhu Hui-Ting,Zhang Qin,Chen Hui-Fen
BackgroundEndometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM.MethodsTRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis.ResultsWe found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin β1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin β1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model.ConclusionIn conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM.
研究领域:
妇科学
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分子生物学
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细胞生物学
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PubMed
高影响因子
CYTOTECHNOLOGY
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2025
·Vol. 77
·期 2
·1-18
·
IF 1.7
Zhou Yi,Luan Fengwu,Feng Xiaonan,Yu Min,Li Lu,Guo Xiaoyan,Yin Xiaolong
Chronic kidney disease (CKD) often progresses to renal fibrosis, which is characterized by excessive extracellular matrix deposition and is also linked to ferroptosis. The present study investigated how TGF-β1 induces ferroptosis and thereby contributes to renal tubular epithelial cell fibrosis. Bioinformatics was employed to identify the differentially expressed genes relevant to renal fibrosis. An in vitro TGF-β1-induced fibrosis model of HK-2 cells was established, and the cell shape index was calculated. Fer-1, NAC, and PD98059 were utilized for targeted intervention, and their mechanisms were verified by transducing cells with WISP1-targeting shRNA lentivirus. Cell morphology was examined under a microscope, and cells were collected to determine the levels of ferroptosis-related factors (Fe 2+ , MDA, GSH, and LPO). Western blotting was performed to measure the levels of ERK1/2, WISP1, and ferroptosis indicators (GPX4 and hyperoxidized PRDX4). Flow cytometry was performed to determine the ROS levels and the rate of cell ferroptosis. TGF-β1 induced the transformation of HK-2 cells into fibroblast-like cells, leading to increased ROS levels, activation of the ERK1/2-WISP1 signaling pathway, and upregulation of ferroptosis and fibrosis-related factors. However, these effects could be effectively inhibited through pretreatment with Fer-1, NAC, and PD98059 individually, which further validated the involvement of the ERK1/2-WISP1 signaling pathway. In addition, WISP1 knockdown suppressed the cell transformation into fibroblast-like cells as well as the ferroptosis process, thereby reducing the expression levels of ferroptosis and fibrosis-related factors. The present study substantiated the process through which TGF-β1 elicits the production of ROS and triggers ferroptosis via the ERK1/2-WISP1 signaling pathway to facilitate the development of renal tubular epithelial cell fibrosis.
研究领域:
细胞生物学
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分子生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF NEUROSCIENCE
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2023
·Vol. 43
·期 16
·2822-2836
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IF 5.3
Jiao Ma,Zhechun Hu,Huimin Yue,Yujian Luo,Chao Wang,Xuan Wu,Yan Gu,Lang Wang
Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown of Grm2 resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused by Grm2 knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided in vivo and in vitro evidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.
研究领域:
神经科学
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分子生物学
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发育生物学
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认知科学
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PubMed
高影响因子
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