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World Journal of Gastroenterology 2003年第4期9卷 784-787页

作者： Hong Shen Guo-Jiang Huang Yue-Wen Gong Departments of Internal Medicine,Biochemistry and Medical Genetics,Faculty of Medicine,University of Manitoba,Winnipeg,Manitoba,Canada John Buhler Research Centre 803G - 715 McDermot Avenue Winnipeg Manitoba Canada R3E 3P4. ygong@ms.umanitoba.ca

AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and ***: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate ***: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.

关键词： Animals Bone Morphogenetic Proteins Cell Differentiation Cell Division Cells, Cultured Liver Male Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't transforming growth factor beta

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

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World Journal of Gastroenterology 2002年第2期8卷 379-381页

作者： Wei-Xing Chen You-Ming Li Chao-Hui Yu Wei-Min Cai Min Zheng Feng-Chen,Department of Gastroenterology, The First Affiliated Hospital,Medical College of Zhejiang University,Hangzhou 310003,Zhejiang Province,China Department of Gastroenterology The First Affiliated Hospital Medical College of Zhejiang University Hangzhou 310003 Zhejiang Province China. weixng121@***

AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, Pbeta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, Pbeta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.

关键词： Humans Liver Diseases, Alcoholic Male RNA, Messenger transforming growth factor beta

Shenqihuatan formula(参七化痰方) reduces inflammation by inhibiting transforming growth factor-beta-stimulated signaling pathway in airway smooth muscle cells

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Journal of Traditional Chinese Medicine 2022年第4期42卷 520-529页

作者： CHEN Jingjing WANG Yuanyuan ZHANG Nianzhi XUE Xiaoming Shanxi Provincial Traditional Chinese Medicine Hospital Taiyuan 030012China Anhui University of Traditional Chinese Medicine Hefei 230038China Department of Respiratory the First Affiliated Hospital of Anhui University of Traditional Chinese MedicineHefei 230031China

OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway ***:The current study examined cell viability using a Cell Counting Kit-8 ***,a Transwell assay was conducted to detect the ability of cell migration,and apoptosis was detected via *** Blot and quantitative real-time polymerase chain reaction(q RT-PCR)were used to determine the expression levels of apoptosis or inflammation-related factors,such as TGF-β,Interleukin-1β(IL-1β),B cell lymphoma 2(Bcl-2),Bcl-2-Associated X(Bax),Ras homolog gene family,member A(Rho A),recombinant rho associated coiled coil containing protein kinase 1/2(ROCK1/2),extracellular regulated protein kinases 1/2(ERK1/2),Snail,and ***,the expression levels of matrix metalloproteinase-9(MMP-9)and Tissue inhibitor of metalloproteinase(TIMP-1)were admeasured by enzyme-linked immuno sorbent ***:The results demonstrated that SQHT inhibited the viability and migration,as well as the the F-actin formation and cytoskeletal reorganization of airway smooth muscle cells(ASMCs)stimulated by TGF-β.By monitoring the changes of critical regulators in the presence of the formula,it was observed that the expression levels of TGF-β,IL-1β,Bcl-2,Rho A,ROCK1/2,ERK1/2,Snail,and Slug were markedly suppressed,whereas Bax expression exhibited the opposite *** with a well-characterized Rho A pathway inhibitor,Fasudil,SQHT generated equivalent or even higher inhibitory effects on these processes in ***:Collectively,these suggested that SQHT can reduce airway inflammation by inhibiting TGF-β-stimulated signaling pathways in *** findings may provide a novel remedy for treating ASMC inflammation,which causes thickening and obstruction of the airway in chronic obstructive pulmonary disease.

关键词： pulmonary disease,chronic obstructive transforming growth factor beta airway inflammation fasudil Shenqihuatan formula

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ROLE OF transforming growth factor β(TGF-β)IN REPAIRING OF BONE DEFECTS

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Chinese Medical Sciences Journal 1996年第4期11卷 209-214页

作者：孙玉鹏张皖清陆裕朴胡蕴玉马富成陈万禄 InstituteofTraumatologyandOrthopaedics XijingHospitaltheFourthMilitaryMedicalUniversityXian710032 DepartmentofMaxillofacialSurgery StomatologicalCollegetheFourthMilitaryMedicalUniversity DepartmentofPathology XijingHospitaltheFourthMilitaryMedicalUniversity

TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.

关键词： transforming growth factor beta bone defects bone repair

Effect of substance P on gene expression of transforming growth factor β-1 and its receptors in rat's fibroblasts

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Chinese Journal of Traumatology 2003年第6期6卷 350-354页

作者：赖西南王正国朱金明王丽丽 Research Institute of Surgery Daping Hospital Third Military Medical University

Objective: To investigate the effect of substance P (SP) on gene expression of transforming growth factor β-1 (TGFβ-1), transforming growth factor receptor-1 (TGFR-1) and transforming growth factor receptor-2 (TGFR-2) in fibroblasts cultured in vitro from rat’s granulation tissues. Methods: The fibroblasts from the granulation tissues in the skeletal muscle of rat’s hind limbs injured by formaldehyde were cultured in vitro. When different concentrations (10 -9-10 -5 mol/L) of SP were added into the culture medium, the changes of gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the cultured fibroblasts were observed with reverse transcription polymerase chain reaction at different intervals (0, 3, 6, 12 and 24 hours after incubation). Results: The gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the fibroblasts cultured from rat’s granulation tissues was up-regulated by SP. The peak level of the mRNA expression was found at 10 -8 mol/L SP and the up-regulation effect was not found at 10 -5 mol/L and 10 -6 mol/L. The peak levels of gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at 6 and 12 hours, respectively. Conclusions: SP has up-regulation effect on the gene expression of TGFβ-1, TGFR-1 and TGFR-2 in fibroblasts from rat’s granulation tissues in vitro, and the effect is related to different stimulating concentrations of SP. It may be concerned with proliferation and differentiation of fibroblasts and formation of scar tissues during wound healing.

关键词： Substance P transforming growth factor beta Receptors, transforming growth factor beta Fibroblasts Scars

PPAR gamma inhibits growth of rat hepatic stellate cells and TGF beta-induced connective tissue growth factor expression

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Acta Pharmacologica Sinica 2006年第6期27卷 715-723页

作者： Kai SUN Qian WANG~2 Xiao-hui HUANG Department of Hepatobiliary Surgery,the First Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510080,China Department of Hepatobiliary Surgery the First Affiliated Hospital of Sun Yat-Sen University Guangzhou China

Aim:To investigate the effect of peroxisome proliferator-activated receptor gamma(PPARγ)activation on the growth of rat hepatic stellate cells(HSC)and trans-forming growth factor beta(TGF-β)-induced connective tissue growth factor(CTGF)***:After being treated with various amounts of thePPARγ natural ligand 15-deoxy-A 12,14-prostaglandin J2(15-d-PGJ2)or syntheticligand GW7845,the status of HSC proliferation and apoptosis were detected byMTT assay and flow ***,HSC were treated with PPARγ-specific antagonist GW9662 prior to the addition of 15-d-PGJ2or GW7845 andwere subsequently stimulated with TGF-β*** mRNA and protein levels ofCTGF expression were detected by semi-quantitative RT-PCR and Western blot-ting *** changes in the HSC were observed by ***:15-d-PGJ2and GW7845 markedly inhibited HSC prolifera-tion and induced cell apoptosis in a dose-dependent ***,PPARγligands significantly suppressed TGF-β1-induced CTGF expression(at both tran-scriptional and post-transcriptional levels)in HSC,and the inhibitory effect wasdramatically,if not completely,abolished by pretreatment with GW9662,sug-gesting that the inhibition was indeed mediated by PPARγ.Moreover,morpho-logical observation revealed that PPARγ activation caused obvious changes ofHSC from activated to quiescent ***:The PPARγligand hasa potent inhibitory effect on the growth of HSC and TGF-β1-induced CTGFexpression,which makes it a potential antifibrotic candidate for the treatment andprevention of hepatic fibrosis.

关键词： PPAR gamma transforming growth factor beta connective tissue growth factor hepatic stellate cells

Clinical impact of plasma TGF-β1 and circulating TGF-β1 mRNA in diagnosis of hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2008年第3期7卷 288-295页

作者： Zhi-Zhen Dong,Deng-Fu Yao,Min Yao,Li-Wei Qiu,Lei Zong,Wei Wu, Xin-Hua Wu,Deng-Bing Yao and Xian-Yong Meng Department of Diagnostics,Research Center of Clinical Molecular Biology,Department of Laboratory Science,and Department of GastroenterologyAffiliated Hospital and Institute of Neurosciences,Nantong University,Nantong 226001,China Department of Diagnostics Affiliated Hospital Nantong University Nantong 226001 China.

BACKGROUND:transforming growth factor-β(TGF-β) plays an important role in the regulation of cell growth and differentiation,angiogenesis,extracellular matrix formation,immunosuppression and cancer development. In this study,we investigated the levels of TGF-β1 and TGF-β1 mRNA expression,their relationship with HBV replication,and their diagnostic value for hepatocellular carcinoma(HCC). METHODS:Total RNAs were extracted from HCC samples and matched non-tumor tissues,and from peripheral blood mononuclear cells in HCC ***-β1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-β1 expression was assessed by *** clinical characteristics were analyzed between TGF-β1 and HBV *** diagnostic value of circulating TGF-β1 and TGF-β1 mRNA levels were investigated in HCC patients. RESULTS:The incidence of hepatic TGF-β1 expression was 83.3%in HCC samples,43.3%in the surrounding tissues, 94.7%in the HBV DNA-positive group,and 63.6%in the HBV DNA-negative *** TGF-β1 expression was associated with the degree of HCC differentiation and the status of HBV replication,but not with the size or number of *** TGF-β1 level and incidence of TGF-β1 mRNA were significantly higher in the HCC groupthan in any group of patients with benign liver disease, with a higher sensitivity of 89.5%and a specificity of 94.0% for HCC diagnosis when circulating TGF-β1 levels were >1.2μg/*** significant correlation was found between TGF-β1 expression and AFP level or tumor *** TGF-β1 level and serum AFP raised the detection rate to 97.4%. CONCLUSIONS:Abnormal expression of hepatic TGF-β1 is associated with the degree of HCC differentiation and HBV *** circulating TGF-β1 and TGF-β1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.

关键词： hepatocellular carcinoma transforming growth factor beta immunohistochemistry diagnosis

GFAP promoter directs lacZ expression specifically in a rat hepatic stellate cell line

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World Journal of Gastroenterology 2006年第5期12卷 723-730页

作者： Gunter Maubach Michelle Chin Chia Lim Institute of Bioengineering and Nanotechnology 31 Biopolis WayThe Nanos#04-01138669Singapore.

AIM： The GFAP was traditionally considered to be a biomarker for neural gila （mainly astrocytes and nonmyelinating Schwann cells）. Genetically, a 2.2-kb human GFAP promoter has been successfully used to target astrocytes in vitro and in vivo. More recently, GFAP was also established as one of the several makers for identifying hepatic stellate cells （HSC）. In this project, possible application of the same 2.2-kb human GFAP promoter for targeting HSC was investigated. METHODS： The GFAP-lacZ transgene was transfected into various cell lines （HSC, hepatocyte, and other nonHSC cell types）. The transgene expression specificity was determined by X-gal staining of the β-galactosidase activity. And the responsiveness of the transgene was tested with a typical pro-fibrotic cytokine TGF-β1. The expression of endogenous GFAP gene was assessed by real-time RT-PCR, providing a reference for the transgene expression. RESULTS： The results demonstrated for the first time that the 2.2 kb hGFAP promoter was not only capable of directing HSC-specific expression, but also responding to a known pro-fibrogenic cytokine TGF-β1 by upregulation in a doseand time-dependent manner, similar to the endogenous GFAP. CONCLUSION： In conclusion, these findings suggested novel utilities for using the GFAP promoter to specifically manipulate HSC for therapeutic purpose.

关键词： Promoter Regions (Genetics) Animals Base Sequence Cell Line DNA, Recombinant Gene Expression Glial Fibrillary Acidic Protein Hepatocytes Humans Lac Operon RNA, Messenger Rats Transfection transforming growth factor beta transforming growth factor beta1

Inhibitory effects of rapamycin on the different stages of hepatic fibrosis

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World Journal of Gastroenterology 2014年第23期20卷 7452-7460页

作者： Yun Jeung Kim Eaum Seok Lee Seok Hyun Kim Heon Young Lee Seung Moo Noh Dae Young Kang Byung Seok Lee Department of Internal Medicine Chungnam National University School of MedicineDaejeon 301-721South Korea Department of Surgery Chungnam National University School of MedicineDaejeon 301-721South Korea Department of Pathology Chungnam National University School of MedicineDaejeon 301-721South Korea

AIM: To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.

关键词： Liver cirrhosis Sirolimus transforming growth factor beta Platelet-derived growth factor Ribosomal protein S6 kinases

Inhibitory Mechanism of Inteferon-gamma on Human Fibroblasts from Tenon's Capsule

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第3期24卷 292-293,299页

作者：韩波胡义珍熊新春 Department of Ophthalmology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Summary: The inhibitory mechanism of interferon-gamma (IFN-γ) on the fibroblasts from Tenon's capsule was studied. By using immunohistochemical SP method and pathological image system, the inhibitory effects of IFN-γ on the expression of transforming growth factor beta receptor I in the in vitro cultured fibroblasts from Tenon's capsule were quantitatively analyzed. The results showed that IFN-γ could reduce the expression of transforming growth factor beta receptor I in the fibroblasts with the following dose-effect relationship: Y=1937.5-134.2 Igx (r=-0.971, Ptransforming growth factor beta receptor I in the fibroblasts from Tenon's capsule. The modulation of the transforming growth factor beta receptor I expression by IFN-γ may be beneficial to the alleviation of the hyperplasia of scar after trabeculectomy.

关键词： interferon-gamma glaucoma transforming growth factor beta receptor fibroblasts