ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Yingying Chen,Wei Song,He Zhang,Xinping Ji
Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a vital process in idiopathic pulmonary fibrosis (IPF), which results in the accumulation of fibroblasts and myofibroblasts and excessive extracellular matrix deposition. Based on RNA sequencing analysis and GEO dataset reanalysis, we screened out MICALL2, a gene upregulated in the lungs of IPF mice and alveolar epithelial type II (ATII) cells from IPF patients, and aimed to explore its role in IPF. We validated the expression of MICALL2 in bleomycin (BLM)-induced IPF mice and TGF-β1-stimulated ATII cells (primary murine ATII cells and A549 cells), and explored the role of MICALL2 in IPF by knockdown of MICALL2 in BLM-induced mice and TGF-β1-stimulated ATII cells. We found that MICALL2 was upregulated in the lungs of BLM-induced mice and TGF-β1-stimulated ATII cells. MICALL2-deficient mice had reduced fibrogenesis and restrained EMT upon BLM challenge. Knockdown of MICALL2 restrained the EMT process, in vitro, through impeding β‐catenin nuclear translocation. Mechanistically, we demonstrated that NPAS2 is directly bound to the promoter of MICALL2. Altogether, our data revealed transactivation of MICALL2 induced by NPAS2, contributing to activation of the Wnt/β-catenin pathway in ATII cells, thus leading to the EMT process and subsequent pulmonary fibrosis. Interfering with MICALL2 may represent an innovative therapeutic target to mitigate the extent of IPF.
研究领域:
肺科学
·
细胞生物学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 13
·e23756
·
IF 4.4
Lishen Shan,Li Chen,Wenxin Shen,Qianlan Zhou,Si Liu,Lina Han,Qinzhen Zhang,Bing Dai,Yuhong Zhao
Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as “airway remodeling”, are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-β1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-β1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-β1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-β1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-β1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.
研究领域:
呼吸病学
·
免疫学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Tianyue Wang,Qianlan Zhou,Yunxiao Shang
Airway remodeling happens in childhood asthma, in parallel with, but not necessarily subsequent to, airway inflammation. The differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal-transition (EMT) is one of the mechanisms underlying airway remodeling. This study aimed at identifying novel molecules involved in pediatric asthma-associated airway remodeling. Asthma model was established by challenging C57BL/6 mouse pups with ovalbumin (OVA). We found that the expression of Cadherin 11 (CDH11), a type II cadherin, was increased by OVA treatments in the airway epithelium. Our earlier microarray data suggested miRNA-451a-5p (miRNA-451a) as a potential regulator of CDH11. In contrast to CDH11, miRNA-451a expression decreased in the asthmatic lung. MiRNA-451a was then packaged into a lentivirus vector and systematically given to the asthmatic pups. Our data indicated that OVA-induced infiltration of inflammatory cells, including eosnophils, neutrophils, macrophages and lymphocytes, was reduced by miRNA-451a over-expression. EMT was initiated in asthmatic mice as demonstrated by increased alpha-smooth muscle actin (α-SMA) positive cells present in airway epithelium, which was inhibited by miRNA-451a. CDH11 elevation in vivo was also inhibited by miRNA-451a. Dual-Luciferase analysis further showed CDH11 as a novel valid target of miRNA-451a. Additionally, in vitro, EMT was triggered in human 16HBE airway epithelial cells by pro-fibrotic transforming growth factor β (TGF-β). Corresponding to the anti-EMT effects observed in vivo , miRNA-451a also inhibited TGF-β-induced collagen deposition in cultured airway epithelial cells by targeting in CDH11. In summary, our study demonstrates that the deregulated miRNA-451a-CDH11 axis contributes to airway remodeling in childhood asthma.
研究领域:
分子生物学
·
呼吸医学
·
儿科
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-17
·
IF 14.919
Xu Minjun,Hu Kaili,Liu Yipu,Huang Yukun,Liu Shanshan,Chen Yu,Wang Dayuan,Zhou Songlei,Zhang Qian,Mei Ni,Lu Huiping,Li Fengan,Gao Xiaoling,Chen Jun
Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.
研究领域:
肿瘤学
·
纳米技术
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 7
·6172
·
IF 5.6
Tianxiao Sun,Haihua Li,Yan Zhang,Guixin Xiong,Yuerun Liang,Fang Lu,Rong Zheng,Qi Zou,Jiejie Hao
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by lung inflammation and excessive deposition of extracellular matrix components. Transforming growth factor-β1 (TGF-β1) induced epithelial–mesenchymal transformation of type 2 lung epithelial cells leads to excessive extracellular matrix deposition, which plays an important role in fibrosis. Our objective was to evaluate the effects of 3-cyclopropylmethoxy-4-(difluoromethoxy) benzoic acid (DGM) on pulmonary fibrosis and aimed to determine whether EMT plays a key role in the pathogenesis of pulmonary fibrosis and whether EMT can be used as a therapeutic target for DGM therapy to reduce IPF. Firstly, stimulation of in vitro cultured A549 cells to construct EMTs with TGF-β1. DGM treatment inhibited the expression of proteins such as α-SMA, vimentin, and collagen Ⅰ and increased the expression of E-cadherin. Accordingly, Smad2/3 phosphorylation levels were significantly reduced by DGM treatment. Secondly, models of tracheal instillation of bleomycin and DGM were used to treat rats to demonstrate their therapeutic effects, such as improving lung function, reducing lung inflammation and fibrosis, reducing collagen deposition, and reducing the expression of E-cadherin. In conclusion, DGM attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats.Keywords:IPF;A549;EMT;TGF-β1/Smad;ECM
研究领域:
药理学
·
呼吸医学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Peng Wei,Zhang Shiwen,Zhou Wei,Zhao Xinchen,Wang Kexue,Yue Chengxu,Wei Xinyu,Pang Siyan,Dong Wei,Chen Sulian,Chen Changjie,Yang Qingling,Wang Wenrui
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
研究领域:
药理学
·
细胞生物学
·
肝病学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Hongzhuan Yin,Di Wu,Qiao Qu,Zhilong Li,Lianrong Zhao
The tumor recurrence and metastasis of colorectal cancer (CRC) are responsible for most of CRC-linked mortalities. It is an urgent need to deeply investigate the pathogenesis of CRC metastasis and look for novel targets for its treatment. The current study aimed to investigate the effects of ubiquitin-specific peptidase 15 (USP-15) on the CRC progression. In vivo, a mouse model of liver metastasis of CRC tumor was established to investigate the role of USP-15. In vitro, the migrated and invasive abilities of CRC cells were assessed by transwell assay. Cell stemness was evaluated by using sphere formation assay. The underlying mechanism was further explored by employing the co-immunoprecipitation, dual luciferase reporter assay, oligonucleotide pull-down assay, and chromatin immunoprecipitation assay. The results showed that USP-15 was upregulated in CRC patients with liver metastasis and high metastatic potential cell lines of CRC. Loss of USP-15 repressed the epithelial-to-mesenchymal transition (EMT), migration, invasion, and stemness properties of CRC cells in vitro. Downregulation of USP-15 reduced the liver metastasis of mice in vivo. USP-15 upregulation obtained the contrary effects. Subsequently, USP-15 deubiquitinated transcription factor AP-4 (TFAP4) and enhanced its protein stability. TFAP4 could transcriptionally activated polycomb group ring finger 1 (PCGF1). The pro-cancer effects of USP-15 were rescue by the knockdown of TFAP4 or PCGF1. In conclusions: USP-15 facilitated the liver metastasis by the enhancement of cell stemness and EMT in CRC, which was at least partly mediated by the deubiquitination of TFAP4 upon the upregulation of PCGF1.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2022
·
IF 10.75
Ling Yang,Jing Yang,Hua Liu,Jingbin Lan,Ying Xu,Xiaobo Wu,Yushan Mao,Dongming Wu,Kejian Pan,Tao Zhang
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Metastasis is a major cause of CRC recurrence and mortality. Several antibiotic drugs have been reported to exert potential anticancer activities, however, whether and how the tetracycline antibiotic minocycline exhibit tumor suppressive effect on CRC remains unknown. Here, we found that minocycline markedly inhibits the epithelial-mesenchymal transition (EMT) process and metastasis of CRC cells both in vitro and in vivo . Using chemical proteomics screening combined with docking analysis and site-directed mutagenesis, we identified LYN as a direct bind target of minocycline, and Ala255 of LYN is required for minocycline binding. Mechanistically, minocycline binding inactivates LYN, leading to STAT3 inactivation and EMT suppression, thereby inhibits CRC metastasis. Tissue microarray analysis further confirmed the clinical relevance of LYN-STAT3 axis in the EMT and progression of CRC. In addition to CRC, minocycline also significantly prevents EMT process and inhibits the metastasis of several other cancer types. Our findings elucidate the mechanism of action of minocycline for the inhibition of CRC metastasis by LYN binding, and suggest that repurposing minocycline may represent a promising strategy for the treatment of advanced CRC and other cancer types.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
·
2025
·Vol. 36
·期 14
·831
·
IF 2.8
Zhao Tianqun,Zeng Tianrui,Jin Shilei,Li Xiaohui,Yu Zhiqiang
BNT (BaO–Nd 2 O 3 –TiO 2 ) system was modified via doping using sol–gel method, and BNST-Mn/PTFE microwave dielectric composite was prepared by mechanical blending. Scanning electron microscopy (SEM), thermal dilatometer, and split post-dielectric resonator (SPDR) were used to characterize the microstructure, dielectric properties, and thermal properties of the composite materials. The results indicate that as the amount of ceramic filler supplied grows, the agglomeration of fillers becomes more pronounced. At a filler content of 10 wt%, the dispersion of the filler in the matrix resin is relatively uniform. The dielectric constant and dielectric loss of the composites increased, and the bonding ability between the two phases diminished with the increase in filler content. When the mass fraction of the ceramic was increased to 70 wt%, the dielectric constant of the composite was 10.92 and the Q·f value was measured at 3584 GHz. At the same time, the coefficient of thermal expansion (CTE) of the composites reached 23 ppm/°C, which was a good compatibility with the copper foil. Lichtenecker equation, Maxwell–Wagner equation, Jayasundere–Smith equation, and effective medium theory equation (EMT) were used to predict the dielectric constant of the composites. In comparison, the dielectric constant values calculated using the EMT equation were in good agreement with the experimental values, especially at low filling volumes. Also, the simulation results of the thermal expansion coefficient of composite materials using the Lichtenecker equation and its improved form are in good agreement with the experimental values.
研究领域:
材料科学
·
陶瓷与复合材料
·
介电材料
·
微波技术
✓ 已验证
产品关联
DOI
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 3
·3192-3196
·
IF 1.39
Meng Zhou,Youli Zhang,Hong Wei,Junbo He,Dawei Wang,Baoding Chen,Jian Zeng,Aihua Gong,Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit‑8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial‑mesenchymal transition (EMT) and the Hippo‑yes‑associated protein (YAP) pathway were detected using western blot analysis. It was revealed that D6R significantly inhibited the proliferation, migration and invasion abilities of SW1990 and PaTu8988 cells. Additionally, D6R led to the upregulation of E‑cadherin (an epithelial marker), and the downregulation of N‑cadherin and vimentin (mesenchymal markers) in SW1990 and PaTu8988 cells. Furthermore, the results of the present study revealed that D6R significantly affected the YAP phosphorylation level and the total YAP protein level, indicating that D6R was functionally involved in the Hippo‑YAP signaling pathway. It has been suggested that D6R‑suppressed EMT in SW1990 and PaTu8988 cells may occur via the Hippo‑YAP pathway and that it may be a feasible drug to ameliorate the malignant phenotype of SW1990 and PaTu8988 cells.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Chenglin Li,Rui Li,Xueyuan Wu,Yifan Zuo,Guixiang Xiong,Meng Huang,Yuqing Sun,Rong Liao,Yang Xiao,Lili Hu,Chao Gao,Yanyan Yu
Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial–mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.
研究领域:
癌症生物学
·
生物医学工程
·
临床肿瘤学
·
分子诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Yuan Zhu,Wei-feng Yin,Pei Yu,Chao Zhang,Ming-hui Sun,Ling-yi Kong,Lei Yang
Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）