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transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

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World Journal of Gastroenterology 2013年第48期19卷 9366-9376页

作者： Marnie J Wood Lawrie W Powell Jeannette L Dixon V Nathan Subramaniam Grant A Ramm Hepatic Fibrosis Group QIMR Berghofer Medical Research Institute Brisbane 4006Australia Faculty of Medicine and Biomedical Sciences The University of Queensland Brisbane 4006 Australia Department of Gastroenterology and Hepatology Royal Brisbane and Women’s HospitalBrisbane 4029 Australia Centre for the Advancement of Clinical Research Royal Brisbane and Women’s Hospital and the University of Queensland Centre for Clinical Research Brisbane 4029 Australia Iron Metabolism Laboratory QIMR Berghofer Medical Research Institute Brisbane 4006 Australia Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane 4006 Australia

AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary ***:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for *** study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease *** was performed using high resolution melt analysis and *** results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron ***:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic *** the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating *** also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes ***,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate ***:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.

关键词： Haemochromatosis Genetic polymorphism Liver fibrosis Toll-like receptor 4 Interleukin 10 Monocyte chemoattractant protein 1 Chemokine(C-C motif) ligand 2 transforming growth factor beta 8-oxoguanine DNA glycosylase

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transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma

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World Journal of Gastroenterology 2018年第25期24卷 2733-2740页

作者： Yang An Song Gao Wen-Chao Zhao Bao-An Qiu Nian-Xin Xia Peng-Jun Zhang Zhen-Ping Fan Department of Hepato-Biliary-Pancreatic Surgery Navy General Hospital of Chinese People’s Liberation Army Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Department of Interventional Therapy Peking University Cancer Hospital & Institute Liver Disease Center for Cadre Medical Care Beijing 302 Military Hospital

AIM To understand the cellular and molecular changes inperipheral blood that can lead to the development of hepatocellular carcinoma(HCC) and provide new methods for its diagnosis and *** Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-β(TGF-β)+ regulatory cells(Tregs) in the peripheral blood was measured, and the expression of TGF-β was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-β(rh TGF-β) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were *** The expression of TGF-β and the percentage of TGF-β+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-β expression group, the high TGF-β expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-β+ Treg groups, suggesting that TGF-β and TGF-β+ Tregs were negatively correlated with the overall survival of the patients. In addition, rh TGF-β promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor *** The results showed that TGF-β may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-β and TGF-β+ Tregs may serve as new markers for predicting a poor prognosis in HCC.

关键词： Hepatocellular carcinoma transforming growth factor-β Regulatory cells Peripheral blood mononuclear cells Interleukin-6

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Effect of Sini decoction on angiotensin Ⅱ, transforming growth factor β_1 and connective tissue growth factor in rats with myocardial fibrosis-induced banding of the abdominal aorta

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Journal of Traditional Chinese Medicine 2018年第3期38卷 427-432页

作者： Shi Yueping Zhai Jianli Liu Chunxiao Department of Traditional Chinese Medicine the First Affiliated Hospital of Jinzhou Medical University Department of Traditional Chinese Medicine Jinzhou Medical University

OBJECTIVE: To investigate the effect of Sini decoction on rats with myocardial fibrosis induced by banding the abdominal aorta, and explore the mechanism underlying its actions on angiotensin Ⅱ(Ang Ⅱ), transforming growth factor-β_1(TGF-β_1)and connective tissue growth factor(CTGF).METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into sham operation, model, Captopril, and Sini decoction groups. The models were established by the partial banding of the abdominal aorta according to Doering's *** weeks later, heart weight indexes were calculated; hemodynamic changes of the hearts were tested; changes in myocardial tissue morphology were observed by Masson staining; and myocardial collagen volume fraction was calculated. Enzyme-linked immunosorbent assay was used to measure the concentration of Ang Ⅱ in serum. The expression of TGF-β_1 and CTGF were determined by immunohistochemistry and Western ***: Compared with the sham operation group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ,and the expression of myocardial TGF-β_1 and CTGF in the model group were significantly increased(P < 0.05). Compared with the model group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ, and the expression of myocardial TGF-β_1 and CTGF in all treatment groups were significantly reduced(P < 0.05).CONCLUSION: Sini decoction reduced AngⅡ level and inhibited the expression of myocardial TGF-β_1 and CTGF, which may explain the mechanism of its protective effect on myocardium with fibrosis.

关键词： Myocardial fibrosis Angiotensin Ⅱ transforming growth factor beta1 Connective tis-sue growth factor Sini decoction

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Wulong Xiaozheng Wan medicated serum inhibits epithelial-mesenchymal transition in human gastric carcinoma cell line BGC823 by modulation of transforming growth factor-β1/Smad signaling

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Journal of Traditional Chinese Medicine 2019年第3期39卷 380-392页

作者： Zhang Yali Wang Bingyu Guo Xueying Yang Lei Li Dandan Yuan Xingxing Department of Gastroenterology Nangang branch of Heilongjiang Academy of Traditional Chinese Medicine Harbin 150006 China Pharmacological Laboratory of Heilongjiang Academy of Traditional Chinese Medicine Harbin 150036China

OBJECTIVE:To evaluate the effect of Wulong Xiaozheng Wan medicated serum on the epithelial-mesenchymal transition (EMT) of BGC823 cell induced by transforming growth factor-β,(TGF-β,) and to explore its ***:EMT model of BGC823 was stimulated by TGF-β*** Xiaozheng Wan medicated serum and LY-364947 were used as *** proliferation and adhesion of BGC823 were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and flow cytometry was used to detect the *** invasion and migration were detected by *** level of matrix metalloproteins was detected by enzyme-linked immunosorbent *** expressions of related proteins and mRNA of EMT marker and TGF-β1/Smad signal pathway were detected by Western blot and reverse transcription-polymerase chain ***:Compared with the TGF-β1 group,Wulong Xiaozheng Wan medicated serum could inhibit the ability of proliferation,heterogeneous adhesion,invasion,and *** also promotes apoptosis and homotypic adhesion in BGC823,with a dose-dependent ***,Wulong Xiaozheng Wan medicated serum could regulate the expression of related proteins and mRNA of TGF-β1/Smad signaling pathway,and inhibit the expressions of EMT transcription factors and EMT ***:Wulong Xiaozheng Wan medicated serum inhibited epithelial-mesenchymal transition by down-regulated the expression of TβRI and the activation of TGF-β1/Smad signaling pathway.

关键词： transforming growth factor beta1 Smad proteins Signal transduction Epithelial-mesenchymal transition Matrix metalloproteinases,secreted BGC823 cell Wulong Xiaozheng Wan

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Effect of intestinal ischemia-reperfusion on expressions of endogenous basic fibroblast growth factor and transforming growth factor β in lung and its relation with lung repair

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World Journal of Gastroenterology 2000年第3期6卷 353-355页

作者： Xiao Bing Fu Yin Hui Yang Tong Zhu Sun Xiao Man Gu Li Xian Jiang Xiao Oing Sun Zhi Yong Sheng Research Laboratory,304th Hospital of PLA,Beijing 100037,China Research Laboratory 304th Hospital of PLA Beijing 100037 China

AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and *** Sixty Wistar rats were divided intofive groups,which underwent sham-operation,ischemia(45 minutes),and reperfusion(6,24and 48 hours,respectively)after ischemia(45minutes).Immunohistochemical method wasused to observe the localization and amounts ofboth growth *** Positive signals of both growthfactors could be found in normal lung,mainly inalveolar cells and endothelial cells of *** and reperfusion insult,expressions ofboth growth factors were increased and theiramounts at 6 hours were larger than those ofnormal control or of 24 and 48 hours after *** The endogenous bFGF and TGF βexpression appears to be up-regulated in thelung following intestinal ischemia andreperfusion,suggesting that both growth factorsmay be involved in the process of lung injury andrepair.

关键词： lung intestinal ischemiareperfusion injury basic fibroblast growth factor transforming growth factor p

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Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

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World Journal of Gastroenterology 2018年第30期24卷 3414-3425页

作者： Bo-Lin Yang Ping Zhu You-Ran Li Min-Min Xu Hao Wang Li-Chao Qiao Hai-Xia Xu Hong-Jin Chen Department of Colorectal Surgery The Affiliated Hospital of Nanjing University of Chinese Medicine

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal *** First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further *** cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β*** addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT ***,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling ***,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell *** In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling ***,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 ***,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of *** These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

关键词： Crohn’s disease Intestinal fibrosis Epithelialto-mesenchymal transition Total flavone of Abelmoschus manihot transforming growth factor-β1/Smad signaling transforming growth factor-β1/non-Smad signaling

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Effect of matrine on transforming growth factor β1 and hepatocyte growth factor in rat liver fibrosis model

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Asian Pacific Journal of Tropical Medicine 2014年第5期7卷 390-393页

作者： Jian-Lan Yu Jun-Hua Li Rong-Gui Cheng Yan-Mei Ma Xiao-Juan Wang Jing-Chun Liu Heji Hospital affiliated to Changzhi Medical School Tumor Hospital of Shanxi Province Shanxi Medical School The First Clinical Hospital of Shanxi Medical School

Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and *** factor(HCF) of liver fibrosis tissue in ***:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after *** rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between ***:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P<0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P<0.05);group D showed a lowest level of TGF-β1,followed by groups C and *** of group B decreased more significantly than A group at weeks 4 and 8(P<0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P<0.05),in which the group D showed the highest level of *** to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious ***:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.

关键词： Liver fibrosis Matrine transforming growth factor β1 Hepatocyte growth factor

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Celastrol inhibits migration, proliferation and transforming growth factor-β2-induced epithelial-mesenchymal transition in lens epithelial cells

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International Journal of Ophthalmology(English edition) 2019年第10期12卷 1517-1523页

作者： Li-Ping Wang Bao-Xin Chen Yan Sun Jie-Ping Chen Shan Huang Yi-Zhi Liu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University

AIM: To investigate the mechanism of celastrol in inhibiting lens epithelial cells(LECs) fibrosis, which is the pathological basis of ***: Human LEC line SRA01/04 was treated with celastrol and transforming growth factor-β2(TGF-β2). Wound-healing assay, proliferation assay, flow cytometry, real-time polymerase chain reaction(PCR), Western blot and immunocytochemical staining were used to detect the pathological changes of celastrol on LECs. Then, we cultured Sprague-Dawley rat lens in medium as a semi-in vivo model to find the function of celastrol ***: We found that celastrol inhibited the migration of LECs, as well as proliferation(P<0.05). In addition, it induced the G2/M phase arrest by cell cyclerelated proteins(P<0.01). Moreover, celastrol inhibited epithelial-mesenchymal transition(EMT) by the blockade of TGF-β/Smad and Jagged/Notch signaling ***: Our study demonstrates that celastrol could inhibit TGF-β2-induced lens fibrosis and raises the possibility that celastrol could be a potential novel drug in prevention and treatment of fibrotic cataract.

关键词： lens cataract fibrosis transforming growth factor-β2 celastrol

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Metformin attenuates angiotensin II induced cardiac fibrosis and transforming growth factor-β1 production through the inhibition of hepatocyte nuclear factor4

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中国药理学通报 2015年第B11期31卷 184-185页

Aim In diabetic patients, metformin appears to provide cardiovascular protection that cannot be attribu- ted only to its antihyperglycemic effects. Metformin is also known as the AMP-activated protein kinase （AMPK） ac- tivator. Our previous study suggested that metformin inhibits transforming growth factor-β1 （TGF-β1） production in a mouse heart failure model of pressure overload. TGF-β1 is a key factor in cardiac fibrosis and is usually induced by Angiotensin Ⅱ （Ang Ⅱ ） in the pressure overload mouse models. This study investigated the effect of metformin on cardiac fibrosis and TGF-β production induced by AngII and the underlying mechanisms. Methods C57/BL6 wild-type and AMPKα2 knockout mice were used. AngII （3 mg · kg-1 · d-1） was infused subcutaneously into mice for 7 days. Adult mouse cardiac fibroblasts were isolated and treated with AngII （ 1 μmol · L-1） and/or met- formin （1 mmol · L-l）. Results In C57/BL6 mice, metformin inhibits AngII-induced cardiac fibrosis. In cardi-ac fibroblasts, metformin inhibits TGF-β1 expression and production induced by AngII. AMPK inhibitor, com- pound C, reversed the effects of metformin. In vivo, AMPKα2 deficiency further increases AngII-induced TGF-β1 production. In cardiac fibroblasts, metformin inhibited AngII induced hepatocyte nuclear factor4 （HNF4ot protein level increase and HNF4α binding with TGF-β1 promoter using chromatin immunoprecipitation assay. In vivo, AMPKα2 deficiency further increased AngII-induced HNF4α protein level. Using HNF4α adenovirus, overexpress- ing HNF4α led to a 1.5-fold increase in TGF-β1 mRNA expression. HNF4a siRNA blocked AngII induced TGF- β1 production. Luciferase reporter with deleted HNF4a binding sites showed decreased TGFbl transcriptional activ- ity induced by AngII. In AMPK or2-/- heart, the inhibition of metformin on HNF4a protein was attenuated. Con- clusion Metformin inhibits AngII induced cardiac fibrosis and TGF-β1 production through AMPK activation. The underlying mechanism is th

关键词： metformin fibrosis angiotensin II transforming growth factor beta1 hepatocyte nuclear factor 4 AMP-activated protein kinases

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Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

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World Journal of Orthopedics 2015年第11期6卷 961-969页

作者： Lorraine A Boakye Keir A Ross John M Pinski Niall A Smyth Amgad M Haleem Charles P Hannon Lisa A Fortier John G Kennedy Department of Orthopaedic Surgery Hospital for Special Surgery Department of Orthopaedic Surgery Rush University Medical Center Department of Clinical Sciences Cornell University College of Veterinary Medicine

AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect ***: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then ***: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.

关键词： Platelet rich plasma transforming growth factor-beta Autologous osteochondral transplantation

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