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Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 387-411 doi: 10.1007/s11684-018-0646-8

摘要：

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

关键词： TGF-β     EMT     lung cancer     pancreatic cancer     latent form     immune function     GARP    

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Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-β1 production from macrophages in mice

CHU Deyong, LI Conglei, SHEN Jilong, WU Qiang

《医学前沿（英文）》 2008年 第2卷 第2期   页码 154-165 doi: 10.1007/s11684-008-0029-7

摘要： In order to investigate the effect of paeoniflorin (PAE) on hepatic fibrosis of mice with and , a model of hepatic fibrosis caused by schistosomiasis was established in mice infected with cercariae of . Then, PAE was orally administered before and after praziquantel treatment and both therapeutics were given simultaneously at different time points after the infection. The concentration of serum hyaluronic acid (HA) was determined by radioimmunoassay (RIA). Hepatic granuloma and fibrosis were evaluated via HE and Masson staining. The expression of ?-smooth muscle actin (?-SMA), transforming growth factor ?1 (TGF-?1) and collagen I (Col I) protein was detected by immunohistochemistry. The effect of soluble egg antigen (SEA) and PAE on the production of TGF-?1 from mouse peritoneal macrophages (PM?s) was investigated by RT-PCR, Western blotting and ELISA. The effect of TGF-?1 in optimum macrophage-conditioned medium (OPMCM) on the proliferation of hepatic stellate cells (HSCs) and collagen secretion from HSCs with anti-TGF-?1 antibody was explored by MTT assay and ELISA. The results show that PAE could significantly reduce the concentration of serum HA, the size of egg granuloma, the severity of hepatic fibrosis and the expression of ?-SMA, TGF-?1 and Col I protein in the pre-treatment group. However, in sim- or post-treatment group, PAE did not have any significant therapeutic effect. TGF-?1 could be secreted from PM?s stimulated by SEA. Meanwhile, the production of TGF-?1 from PM?s could be depressed significantly by PAE in a concentration-dependent manner. TGF-?1 could promote the proliferation of HSCs and the secretion of collagens. In a word, PAE can prevent hepatic granuloma and fibrosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-?1 from PM?s, the proliferation and activation of HSCs and the secretion of collagens from HSCs.

关键词： cercariae     collagen     hyaluronic     OPMCM     soluble    

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initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β

《医学前沿（英文）》 doi: 10.1007/s11684-023-1010-1

摘要： Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

关键词： exosomes induce activation     impair function CD19     exosomal CD19 antigen    

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Genome-wide search for candidate genes determining vertebrae number in pigs

Longchao ZHANG, Jingwei YUE, Xin LIU, Jing LIANG, Kebin ZHAO, Hua YAN, Na LI, Lei PU, Yuebo ZHANG, Huibi SHI, Ligang WANG, Lixian WANG

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 327-334 doi: 10.15302/J-FASE-2017163

摘要： Longer porcine carcasses may be expected to have more vertebrae. Therefore, vertebrae number in pigs is an economically important trait. To examine the genetic basis of this trait, we genotyped 578 F Large White × Minzhu pigs using the Porcine SNP60K BeadChip. A genome-wide association study (GWAS) identified 36 significant single nucleotide polymorphisms (SNPs) on the chromosomes SSC1 (294.28–300.32 Mb) and SSC7 (102.22–109.39 Mb). A 6.04-Mb region that contained all 13 significant SNPs on SSC1 also contained the gene , previously reported to influence the number of vertebrae in pigs. However, the reported putative casual mutation of c.748C>T showed no genome-wide significant association with the trait, suggesting it was not a causal mutation in our population. The remaining 23 significant SNPs on SSC7 were concentrated in a 7.17-Mb region, which was within a quantitative trait locus interval for number of vertebrae. was the closest gene to the most significant SNP and might be a candidate. Haplotype sharing and block analysis refined the QTL to an interval of about 3 Mb containing 29 candidate genes. Of these 29 genes, the previously reported possible casual mutation of g.19034A>C was not found to be a causal mutation in our population. Exploration of these genes via additional genetic and functional studies in mammals revealed that could be a good candidate on SSC7. A mutation of c.1749G>A was detected by GWAS and could be proposed as a candidate causal mutation, or as closely linked to a causal mutation, for the number of vertebrae in pigs.

关键词： genome-wide association study     number of vertebrae     pig     SSC7     TGFβ3    

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Zfyve16 regulates the proliferation of B-lymphoid cells

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren

《医学前沿（英文）》 2018年 第12卷 第5期   页码 559-565 doi: 10.1007/s11684-017-0562-3

摘要：

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16KO) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of T cells in the peripheral blood of Zfyve16KO mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16KO mice. The proliferation potential of Zfyve16KO B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.

关键词： Zfyve16     endofin     hematopoiesis     TGF-β     lymphocytes    

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Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis through inhibition of transforming growth factor β-induced Smad signaling

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 445-455 doi: 10.1007/s11684-014-0378-3

摘要：

Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this study was to investigate the effects of PDE5 inhibitor on cardiac fibrosis. We assessed cardiac fibrosis and pathology in mice subjected to transverse aortic constriction (TAC). Oral sildenafil, a PDE5 inhibitor, was administered in the therapy group. In control mice, 4 weeks of TAC induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation to myofibroblasts). Sildenafil treatment markedly prevented TAC-induced cardiac dysfunction, cardiac fibrosis and cardiac fibroblast activation but did not block TAC-induced transforming growth factor-β1 (TGF-β1) production and phosphorylation of Smad2/3. In isolated cardiac fibroblasts, sildenafil blocked TGF-β1-induced cardiac fibroblast transformation, proliferation and collagen synthesis. Furthermore, we found that sildenafil induced phosphorylated cAMP response element binding protein (CREB) and reduced CREB-binding protein 1 (CBP1) recruitment to Smad transcriptional complexes. PDE5 inhibition prevents cardiac fibrosis by reducing CBP1 recruitment to Smad transcriptional complexes through CREB activation in cardiac fibroblasts.

关键词： PDE5     cardiac fibrosis     TGF-β     CREB    

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Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

《化学科学与工程前沿（英文）》 2007年 第1卷 第4期   页码 343-348 doi: 10.1007/s11705-007-0062-0

摘要： An oxetane-derived monomer, 3-acryloyloxymethyl-3′-methyloxetane (AMO) was prepared from the reaction of 3-hydromethyl-3-methyloxetane with acryloyl chloride. The cationic ring-opening copolymerization of AMO with another oxetane-derived monomer, 3-(2-(2-(2-methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane (MEMO) was conducted in CHCl solution using BF3 ·OEt/1, 4-butanediol as a co-initiator. The resulting copolymers were characterized by FTIR, H NMR and Gel Permeation Chromatography (GPC) analyses, and it was found that the enchained ratio of AMO in the copolymers is far lower than its feed ratio. They were crosslinked via the radical polymerization of the vinyl group initiated by BPO after doping with lithium trifluoromethanesulfonimide (LiTFSI) to give rise to tough polymeric electrolyte films. The ionic conductivity was measured at varying content of AMO and different concentration of lithium salt LiTFSI by AC impedance, and a maximum ion conductivity of 1.44×10 S/cm at 30°C or 1.25×10 S/cm at 80°C was attained in the sample PAM 33 at the mole ratio of O : Li = 20. The DSC results indicated that decreases with the increase of the proportion of AMO in the copolymer, well consistent with the ion conductivity trend. The TGA (thermogravimetric analysis) measurement revealed that this kind of copolymer electrolytes is more thermostable than their liquid counterparts.

关键词： 4-butanediol     2-methoxyethylenoxy     consistent     oxetane-derived     copolymer    

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Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

《医学前沿（英文）》 2008年 第2卷 第1期   页码 95-99 doi: 10.1007/s11684-008-0017-y

摘要： Schistosomiasis japonica, a zoonosis caused by , is endemic to the Philippines and China. Several vaccine candidates have been identified and tested in different animal models, but it is still unclear which will be optimal for testing in the field. Therefore, new antigens and strategies are necessary for vaccine development against schistosomiasis japonica. The Sj14-3-3 gene was amplified and subcloned into the expression vector pPICZ?-B and transformed into X-33 by electroporation. Three transformants were induced with methanol. The cultural supernatant was collected and tested by SDS-PAGE and Western blotting. The protein of rSj14-3-3 was prepared and purified and BALB/c mice were immunized which was followed by a challenging infection. The immuno-protection was then evaluated. The Sj14-3-3 gene was expressed and secreted into the medium and its molecular weight was about 35000 as determined by SDS-PAGE. Western blotting showed that the protein had a high specificity against mouse-anti-Sj14-3-3 monoclonal antibody and rSj14-3-3 had a promising immune reactivity. The results of the immuno-protective experiments revealed that the worm reduction was 26.0%, 32.2%, and 36.8%, respectively. The number of eggs in liver tissue was reduced by 36.8%, 43.2%, and 46.1%, respectively. The recombinant Sj14-3-3 of eukaryotic expression in was successfully harvested. The molecular vaccine of Sj14-3-3 could partially induce resistance to the infection with in BALB/c mice. The recombinant protein Sj14-3-3 has promising immunological potentials for further approach to the diagnosis and development of molecular vaccine.

关键词： development     challenging     rSj14-3-3     resistance     cultural supernatant    

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第四届高性能编译、计算和通信国际会议(HP3C 2020)

会议日期： 2020年03月12日

会议地点： 广东广州

主办单位： HP3C 2020

作为免疫疗法靶点的FOXP3及其辅因子 Review

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

《工程（英文）》 2019年 第5卷 第1期   页码 115-121 doi: 10.1016/j.eng.2019.01.001

摘要：

叉头框蛋白P3（FOXP3）是调节性T细胞（Tregs）的一个主要调节因子，调节性T细胞是能抑制抗原特异性免疫反应的T 细胞亚群，在增强宿主耐受性和维持免疫平衡方面发挥着重要作用。众所周知，FOXP3 与多种蛋白质形成复合物，并能通过乙酰化、磷酸化、泛素化和甲基化等各种翻译后修饰（PTM）进行调节。因此，翻译后修饰可改变FOXP3 的稳定性及其调节基因表达的能力，并最终影响调节性T细胞活性。虽然FOXP3 自身并非理想的药物靶点，但脱乙酰酶、乙酰转移酶、激酶和其他可调节FOXP3 的翻译后修饰的酶均为调控FOXP3 和调节性T细胞活性的潜在靶点。但FOXP3 并非这些酶的唯一底物；因此，当使用相关抑制剂时，必须考虑是否存在有害的“FOXP3脱靶”副作用。

关键词： 调节性T细胞     叉头框蛋白P3（FOXP3）     翻译后修饰     自体免疫     癌症    

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Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1003-0

摘要： Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词： Lipin3     Lipin1     hypertriglyceridemia     obesity     mitochondrial dysfunction    

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关于3D打印技术在医学模具以及再生组织和器官方面的应用综述

Kan Wang, Chia-Che Ho, Chuck Zhang, Ben Wang

《工程（英文）》 2017年 第3卷 第5期   页码 653-662 doi: 10.1016/J.ENG.2017.05.013

摘要： 随着三维（3D）打印和3D 生物打印技术的快速发展，许多研究人员已经开始使用增材制造技术来生产具有多种功能的医学模具。本文综述了3D 打印和3D 生物打印技术在制作功能性医学模具和生物结构方面的应用。特别讨论了3D 打印功能性医学模具（即组织模拟医学模具、放射性医学模具和生理医学模具）及被用于再生组织和器官的3D 生物打印模具的制备（即混合模式支架材料、可转换支架和集成传感器）工艺、发展现状以及未来发展趋势

关键词： 3D打印     3D生物打印     医学模具     再生组织/器官     支架    

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2020第四届环境与能源工程国际会议(IC3E 2020)

会议日期： 2020年03月12日

会议地点： 海南海口 三亚

主办单位： APISE

Influence and related mechanism of Retn gene expression on glucose uptake in 3T3-L1 cells

LI Yahui, DONG Shiyuan, YU Chao, JIANG Yu, LI Huaixing, SUN Shuhan

《医学前沿（英文）》 2007年 第1卷 第3期   页码 269-273 doi: 10.1007/s11684-007-0051-1

摘要： The aim of this article was to investigate the influence and the related mechanism of the gene on glucose uptake and insulin resistance in 3T3-L1 cells. Radioimmunoassay was used to determine glucose uptake in 3T3-L1 cells with different gene expression levels, whether cells were stimulated by insulin or not. RT-PCR and real-time RT-PCR analysis were used to determine the mRNA levels of several glucose transport proteins in 3T3-L1 cells with different gene expression levels, including insulin receptor substrate-1(IRS-1), phosphatidylinositol 3-kinase (PI-3K), AKT-2, glucose transporter-4 (GLUT-4), p38 mitogen-activated protein kinase (p38MAPK) and glycogen synthase kinase-3b (GSK-3). The glucose uptake decreased with the increase in gene expression in 3T3-L1 cells, which was independent of whether the cells were stimulated by insulin or not. The mRNA expression of two signal proteins PI-3K and AKT-2 decreased and the other two signal proteins, GSK-3 and p38MAPK, increased with overexpression in 3T3-L1 cells. Resistin could induce insulin resistance in adipocytes, which might be related to the changes of some proteins in PI-3K and Ras pathways.

关键词： 3T3-L1     influence     resistance     receptor substrate-1     transport    

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标题 作者 时间 类型 操作

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

期刊论文

Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-β1 production from macrophages in mice

CHU Deyong, LI Conglei, SHEN Jilong, WU Qiang

期刊论文

initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β

期刊论文

Genome-wide search for candidate genes determining vertebrae number in pigs

Longchao ZHANG, Jingwei YUE, Xin LIU, Jing LIANG, Kebin ZHAO, Hua YAN, Na LI, Lei PU, Yuebo ZHANG, Huibi SHI, Ligang WANG, Lixian WANG

期刊论文

Zfyve16 regulates the proliferation of B-lymphoid cells

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren

期刊论文

Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis through inhibition of transforming growth factor β-induced Smad signaling

null

期刊论文

虞晓含：中医话健康，食补改善免疫力（2020年3月1日）

2022年04月18日

会议视频

Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

期刊论文

Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

期刊论文

第四届高性能编译、计算和通信国际会议(HP3C 2020)

2020年03月12日

会议信息

作为免疫疗法靶点的FOXP3及其辅因子

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

期刊论文

关于3D打印技术在医学模具以及再生组织和器官方面的应用综述

Kan Wang, Chia-Che Ho, Chuck Zhang, Ben Wang

期刊论文

2020第四届环境与能源工程国际会议(IC3E 2020)

2020年03月12日

会议信息

Influence and related mechanism of Retn gene expression on glucose uptake in 3T3-L1 cells

LI Yahui, DONG Shiyuan, YU Chao, JIANG Yu, LI Huaixing, SUN Shuhan

期刊论文