JOURNAL OF BIOLOGICAL CHEMISTRY
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2021
·Vol. 297
·期 4
·
IF 5.157
Ge Liu,Rui Liu,Yeqi Shan,Chaomin Sun
Many natural polysaccharides have significant anticancer activity with low toxicity, but the complex chemical structures make in-depth studies of the involved mechanisms extremely difficult. The purpose of this study was to investigate the effect of the marine bacterial exopolysaccharide (exopolysaccharide 11 [EPS11]) on liver cancer metastasis to explore the underlying target protein and molecular mechanism. We found that EPS11 significantly suppressed cell adhesion, migration, and invasion in liver cancer cells. Proteomic analysis showed that EPS11 induced downregulation of proteins related to the extracellular matrix–receptor interaction signaling pathway. In addition, the direct pharmacological target of EPS11 was identified as collagen I using cellular thermal shift assays. Surface plasmon resonance and pull-down assays further confirmed the specific binding of EPS11 to collagen I. Moreover, EPS11 was shown to inhibit tumor metastasis by directly modulating collagen I activity via the β1-integrin–mediated signaling pathway. Collectively, our study demonstrated for the first time that collagen I could be a direct pharmacological target of polysaccharide drugs. Moreover, directly targeting collagen I may be a promising strategy for finding novel carbohydrate-based drugs.
研究领域:
癌症生物学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2023
·
IF 5
Jingchen Gao,Xiyuran Wang,Xiangyi Kong,Xujin Yao,Jinyang Ren,Shujun Chen,Na Shen,Zhuo Li,Yitian Wang,Ye Wei,Oleg Glebov,Fengyuan Che,Qi Wan
Proline, a nonessential amino acid, has been demonstrated to possess neuroprotective capabilities in the central nervous system (CNS). However, the mechanisms through which it impacts cerebral ischemia–reperfusion (I/R) injuries remain unclear. Our study observed a decrease in proline concentrations within the ischemic brain tissues of I/R mice. Supplementing proline protected against ischemic neuronal death, both in vivo and in vitro, suggesting its potential as a neuroprotectant. However, our data indicated that proline has a low permeability to the blood–brain barrier (BBB) in mice. Therefore, it is clinically infeasible to develop proline as a stroke therapy. To develop an approach to deliver proline into the injured brain, we engineered a method to transport proline to the injured brain. We prepared chitosan nanoparticles (NPs) loaded with proline utilizing the ion cross-linking method. Our findings demonstrated that the proline-loaded chitosan NPs efficiently passed through the BBB and delivered proline into the injured brain, thereby conferring neuroprotection. Further exploration revealed that proline upregulated the level of annexin A6 (ANX6)/β1 integrin, which, in turn, increased the phosphorylation of cell-survival-promoting kinase Akt. This sequence of events consequently promotes neuronal survival following I/R. In conclusion, our study has developed a neuroprotection approach by which low-BBB-permeable proline is delivered by chitosan NPs into the brain. Furthermore, this study suggests that the neuroprotective role of proline in I/R is mediated by the ANX6/β1 integrin/Akt signaling pathway.
研究领域:
神经科学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2016
·
IF 4.32
Yunzhu Qian,Hanbang Chen,Yang Xu,Jianxin Yang,Xuefeng Zhou,Feimin Zhang,Ning Gu
Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES) nanofibrous architecture and collagen I (COL I)-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid)/poly(caprolactone) (PLGA/PCL; 7:3 w/w) was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell growth. Analysis of β1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced surface activity by 3,4-dihydroxyphenylalanine-assisted modification and COL I incorporation of PLGA/PCL electrospun membranes could successfully fill osteogenic defects and allow for better cell proliferation and differentiation.
研究领域:
生物材料
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组织工程
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2020
·Vol. 305
·期 4
·1900759
·
IF 3.853
Tingting Yu,Ke Hu,Qiufan Xu,Xueqin Xu,Chunyue Du,Yinyi Zhao,Sen Yan,Wei Wang,Shijia Tang,Shen Yue,Xiya Zhang,Danlei Wang,Feimin Zhang,Steven Yan Cheng,Ning Gu
The biophysical factors of microenvironments have increasingly been recognized as playing key roles in driving cell functions along with biochemical cues. However, current synthetic extracellular matrix materials with tunable biophysical properties are both costly and technically complicated to prepare, therefore limiting their application in the molecular biology field. Herein, an interpenetration hydrogel group with gradient stiffness and cell anchor points is developed, and the matrix stiffness and adhesion property functions as key regulators to determine the final output of Sonic Hedgehog (Shh) signaling is reported. Specifically, it is shown that the spreading areas of mouse embryonic fibroblasts are mainly regulated by stiffness of the matrix. The Shh-induced Gli1 expression also increases with the cell spreading area. Finally, this work shows that b1-integrin and focal adhesion kinase, respectively, act as sensors of matrix stiffness and adhesion properties, demonstrating the significance of the precise regulation of Shh signaling by cellular microenvironments. These results demonstrate the feasibility of using this hydrogel platform to study the impact of biophysical changes of the microenvironment on particular cellular signal pathways, and can potentially be applied in low-cost, high throughput screening of signal pathways which are responsive to the biophysical changes of microenvironments.
研究领域:
生物材料
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细胞生物学
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分子生物学
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生物物理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）