Molecular Medicine Reports
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2015
·Vol. 12
·期 6
·7992-8002
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IF 1.554
Xu‑Dong Cheng,Jun‑Fei Gu,Jia‑Rui Yuan,Liang Feng,Xiao‑Bin Jia
The migration and invasion of lung cancer cells into the extracellular matrix contributes to the high mortality rates of lung cancer. The protein kinase C (PKC) and downstream signaling pathways are important in the invasion and migration of lung cancer cells. Calycosin (Cal), an effector chemical from Astragalus has been reported to affect the recurrence and metastasis of cancer cells via the regulation of the protein expression of matrix metalloproteinases (MMPs). The inhibition of Cal on the migration and invasion of A549 cells was investigated in the present study. Cell viability and apoptosis assays were performed using MTT and flow cytometric analyses. A wound healing assay and Transwell invasion assay were performed to evaluate the effect of Cal on A549 cell migration and invasion. Invasion‑associated proteins, including MMP‑2, MMP‑9, E‑cadherin (E‑cad), integrin β1, PKC‑α and extracellular signal‑regulated kinase 1/2 (ERK1/2) were detected using western blotting. In addition, PKC‑α inhibitor, AEB071, and ERK1/2 inhibitor, PD98059, were used to determine the association between the suppression of PKC‑α /ERK1/2 and invasion, MMP‑2, MMP‑9, E‑cad and integrin β1. Cal was observed to suppress cell proliferation and induce apoptosis. There were significant differences between the phorbol‑12‑myristate‑13‑acetate (TPA)‑induced A549 cells treated with Cal and the untreated cells in the rates of migration and invasion. The levels of MMP‑2, MMP‑9, E‑cad and integrin β1 in the TPA‑induced A549 cells changed markedly, compared with the untreated cells. In addition, the suppression of Cal was affected by the PKC inhibitor, AEB071, an ERK1/2 inhibitor, PD98059. The results of the present study indicated that Cal inhibited the proliferation, adhesion, migration and invasion of the TPA‑induced A549 cells. The Cal‑induced repression of PKC‑α/ERK1/2, increased the expression of E‑Cad and inhibited the expression levels of MMP‑2, MMP‑9 and integrin β1, which possibly demonstrates the mechanism underlying the biological anticancer effects of Cal.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
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
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
JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Tianxin Zhao,Xiangliang Tang,Dian Li,Jinglu Zhao,Rui Zhou,Fangpeng Shu,Wei Jia,Wen Fu,Huimin Xia,Guochang Liu
Polybrominated diphenyl ethers (PBDEs) are a widely used class of brominated flame retardants . Exposure to PBDEs could induce testicular damage in mammals, but the effects and potential mechanism of action of prenatal exposure to environmentally relevant PBDEs on testicular development remain unclear. For the in vivo study, pregnant ICR mice were exposed to environmentally relevant levels of 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99), a major component of commercial PBDE mixtures. We found that the anogenital index and testicular organ coefficient were significantly decreased, the incidence of cryptorchidism was increased, and testicular histology was disturbed in male offspring . Transcriptomic profiling showed that steroidogenesis disorders were significant in all PBDE-99 exposure groups. The testosterone levels, expressions of testosterone regulators, and the number of CYP11A1-positive and 11β-HSD1-positive Leydig cells were significantly decreased after PBDE-99 exposure. For the in vitro study, TM3 Leydig cells were exposed to PBDE-99 at gradient concentrations. Transcriptomic profiling and validation experiments showed that PBDE-99 upregulated reactive oxygen species , activated the ERK1/2 pathway, inhibited the ubiquitination degradation pathway, and finally induced Leydig cell apoptosis. Cumulatively, these findings revealed that prenatal exposure to environmentally relevant levels of PBDE-99 leads to steroidogenesis disorders by inducing the apoptosis of Leydig cells, causing testicular dysgenesis.
研究领域:
毒理学
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生殖生物学
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环境健康
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Jiayu Lin,Long Liu,Shan Huang,Weijia Zheng,Haoming Liu,Zhenzu Bai,Kai Jiang,Xiaoyan Wang
Mesoporous bioactive glass (MBG) is a potential biomedical material in bone defect repairment because of its bioactivity, biocompatibility, and osteoinduction properties. Here we report that Mg-doped MBG scaffold with 3:1 Ca/Mg ratio (MBG-Ca/Mg-3) is good for MC3T3-E1 osteoblast differentiation and mineralization. Mimicking bone extracellular matrix structure by electrospinning, we used MBG-Ca/Mg-3 adsorbed with Osteocalcin-Osteopontin-Biglycan (OOB), a new unique matrix fusion protein, to form [email protected] /Mg-3 scaffold, which has multifunctional ability in calvarial bone defect repairment in vivo . Intriguingly, we found that [email protected] /Mg-3 scaffold increases the expression of osteoblastic marker genes, including bone morphogenetic protein ( Bmp2 ), osteopontin ( Opn ), Osterix , Runx2 through activation of ERK1/2. We concluded that [email protected] /Mg-3 scaffold promotes osteoblast differentiation and mineralization through ERK1/2 pathway and it can also enhance bone formation in vivo , which provides a new biomaterial in bone tissue engineering.
研究领域:
生物医学工程
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材料科学
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组织工程
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生物材料
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Tiancheng Li,Mengmeng Shu,Cheng Zhu,Yixin Li,Qicheng Liu,Zhiyu Zhu,Yangyang Jiang,Peng Mei,Yu Jin,Bing Fang,Lunguo Xia
In osteoarthritic chondrocytes, dysregulation of mitochondrial dynamics due to excessive intracellular reactive oxygen species (ROS) under inflammatory conditions is a significant contributory factor to poor treatment outcomes, because it leads to a reduced cell response to chondrogenic drugs during this state. The aim of this study was to develop a multifunctional Au@CeO 2 yolk-shell nanozyme (YSN) as a novel therapeutic nanomaterial and drug delivery system. Under photothermal conditions, Au@CeO 2 nanozymes neutralized excessive ROS, enhanced antioxidant capacity, and maintained mitochondrial homeostasis of osteoarthritic chondrocytes, thereby restoring cellular responsiveness to external stimuli. Furthermore, bioactive peptide CK2.1 loaded in YSNs (Au@CeO 2 -CK2.1) achieved ordered release under photothermal conditions, effectively promoting chondrocyte anabolic activity. In a mice osteoarthritis (OA) model, local Au@CeO 2 -CK2.1 photothermal therapy effectively enhanced cartilage repair and regeneration in vivo . Mechanically, our research uncovers that decreased chondrogenic drug response is associated with activation of extracellular regulated kinase-1 and -2 (ERK1/2) pathway, and Au@CeO 2 -CK2.1 YSNs regulates mitochondrial dynamics through inhibiting ERK1/2 and dynamin-1-like protein (DRP1) phosphorylation. The results of this study demonstrated an effective therapeutic strategy that rescued chondrogenic drug response in osteoarthritic chondrocytes, achieving anti-inflammation and cartilage regeneration.
研究领域:
纳米技术
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生物材料
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药物递送系统
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再生医学
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骨科
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细胞生物学
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DOI
高影响因子
PHYTOMEDICINE
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2020
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IF 4.268
Xiaotian Qi,Jing Liu,Xiaoyu Li,Mengyue Fan,Nana Huang,Rong Sun
Background Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical, cancer chemotherapy induced neutropenia (CCIN) infection and infection-related mortality is high for lack of functionally mature neutrophils . Generating functional neutrophils is new therapeutic approaches to reduce CCIN-associated infection and mortality. Saikosaponin a (SSA) is one of the major bioactive components of Radix Bupleuri (RB) and exerts immunoregulatory effects. Purpose The present study aims to investigate the efficacy and mechanism of SSA in CCIN therapy. Methods SSA was applied both in vitro and in vivo to assess the efficacy of CCIN therapy. The differentiation of neutrophils was measured by Nitroblue tetrazolium (NBT) reduction assay and Giemsa staining assay. The neutrophil differentiation related real-time transcription factors were detected by quantitative PCR (RT-qPCR) and Western Blot . Bacteria killing assay was used to assess the ability of fighting infection. Network pharmacology was employed to explore the mechanism network, and the predicted pathways were validated by Western Blot. Results We found that SSA contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo . Network pharmacology prediction showed 55 pathways were predicted involved in SSA against CCIN. Further validation showed that CBL-ERK1/2 pathway was activated by SSA, which could upregulate PU.1 and CEBPβ expression leading to neutrophil differentiation. Conclusions Our findings suggest a natural regimen SSA regenerates microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2 pathway, providing a rationale for future therapeutic approaches.
研究领域:
药理学
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肿瘤学
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免疫学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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