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

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《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    

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    

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    

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

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《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    

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    

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    

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

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

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

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

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