1.Distribution and expression of transforming growth factor beta and their receptors in hypertrophic scar.
Luo LU ; Yu-lin CHEN ; Qing-guo ZHANG
Chinese Journal of Burns 2004;20(1):30-33
OBJECTIVETo explore the role of transforming growth factor beta (TGF beta) and their receptors (TGF beta-R) in the pathogenesis of hypertrophic scar.
METHODSSpecimens of normal skin and hypertrophic scar were harvested and the distribution and the expression of the TGF beta and TGF beta-R were determined by immunohistochemistry and in situ hybridization method.
RESULTSThe expressions of TGF beta and TGF beta-RII in normal skin were higher than the expression of TGF beta 1, TGF beta 2 and TGF-RI. But in hypertrophic scar the results were on the contrary. The mRNA expressions of TGF beta 1, TGF beta 2 and TGFRI were evidently increased with decreased mRNA expression of TGF-beta 3 and TGFR II in the hypertrophic scar when compared with those in the normal skin.
CONCLUSIONThe expression of TGF-beta (beta 1, beta 2, beta 3) and their receptors in different levels during the process of wound healing might be related to the formation of hypertrophic scars.
Cicatrix, Hypertrophic ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; RNA, Messenger ; genetics ; metabolism ; Receptors, Transforming Growth Factor beta ; genetics ; metabolism ; Skin ; metabolism ; pathology ; Transforming Growth Factor beta ; genetics ; metabolism
2.Role of TGF-beta1 and TGF-beta Type II Receptor in Gastric Cancer.
Dong Il PARK ; Hee Jung SON ; Sang Yong SONG ; Won Hyeok CHOE ; Yun Jeong LIM ; Sang Jong PARK ; Jae J KIM ; Young Ho KIM ; Poong Lyul RHEE ; Seung Woon PAIK ; Jong Chul RHEE ; Kyoo Wan CHOI
The Korean Journal of Internal Medicine 2002;17(3):160-166
BACKGROUND: TGF - beta is known as a cell growth inhibitory factor to suppress almost all cells, including the epithelial cell. Unlike normal cells, cancer cells are not affected by TGF- beta growth inhibitory action and the lack of TGF- beta receptor expression or mutation is being reported as its mechanism, which is rarely studied in Korea. Therefore, we investigated this study to clarify the role of TGF - beta I and TGF - beta II receptors in gastric cancer. METHODS: 23 cases that underwent operations for gastric cancer provided RNA collected from their carcinoma tissues and adjacent normal tissues. We investigated the level of TGF - beta 1 and T beta R-II mRNA expression with semi- quantitatively reverse transcription PCR and analyzed the correlation with prognostic factors, such as tumor size, depth of invasion, tumor differentiation and lymph-node metastasis. RESULTS: (1) TGF- beta I and T beta R-II mRNA were expressed in all carcinoma tissues and adjacent normal tissues of the 23 cases without statistical difference in the level of the expression. (2) The level of TGF - beta 1 mRNA expression was higher in patients with gastric cancer invaded only at the mucosa and submucosa than in patients with gastric cancer invaded over muscular propria, and also higher in the patients without lymph-node metastasis or perineural invasion than in the patients with lymph-node metastasis or perineural invasion. There was no significant correlation between the level of T beta R-II mRNA expression and several parameters, such as age, gender, tumor size, location, differentiation, Lauren's classification and vascular invasion. (3) There was a significant correlation between the level of TGF - beta 1 and T beta R-II mRNA expression in carcinoma tissues. CONCLUSION: It indicated that TGF - beta 1 mRNA expression in gastric cancer might concern the early stage of gastric carcinogenesis and, unlike the earlier reports, it was higher in patients with early gastric cancer, negative lymph-nodes or negative perineural invasion. Further studies are required to clarify the role of TGF - beta 1 in gastric carcinogenesis with more patients.
Female
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Human
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Male
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Middle Age
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Prognosis
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RNA, Messenger/genetics/metabolism
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Receptors, Transforming Growth Factor beta/*genetics
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Stomach Neoplasms/*genetics/metabolism
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Transforming Growth Factor beta/metabolism
3.Antitumor effect of natural killer cells in vitro by blocking transforming growth factor-β signaling.
Bo YANG ; Hui LIU ; Li-ya ZHANG ; Jin-yu LI ; Li BAI ; Sheng-jie SUN ; Shun-chang JIAO
Acta Academiae Medicinae Sinicae 2010;32(4):433-437
OBJECTIVETo investigate the antitumor effect of natural killer (NK) cells on human colorectal cancer cells HT-29 in vitro by blocking transforming growth factor-β (TGF-β) signaling in NK cells transfected with vector containing dominant negative TGF-β type 2 receptor (DNTβR2).
METHODSTGF-β1 was added at the final concentration of 10 ng/ml for HT-29 cells. Primary NK cells were transfected with recombinant plasmid pIRES2-AcGFP-DNTβR2 and control plasmid pIRES2-AcGFP using Amaxa Nucleofector technology respectively. The cytotoxicity of these two types of NK cells to HT-29 cells was detected and analyzed by cell counting kit-8.
RESULTSThe transfection efficiency of primary NK cells was 18.85% for the plasmid pIRES2-AcGFP-DNTβR2 and 35.28% for the control plasmid pIRES2-AcGFP. The expression of DNTβR2 in NK cells was confirmed by Western blotting and RT-PCR. Primary NK cells displayed significantly lower cytotoxicity against HT-29 cells incubated with TGF-β1 than that without TGF-β1 (effect-target cell ratio 10:1,14.40%∓ 2.00% vs. 26.14% ∓ 2.50%, P > 0.05; effect-target cell ratio 20:1, 19.18% ∓ 2.49% vs. 40.81% ∓ 3.50%, P > 0.05). The cytotoxicity of NK cells transfected with DNTβR2 vector was significantly higher than that with control vector against HT-29 cells cultured with 10 ng/ml TGF-β1 (effect-target cell ratio 10:1, 21.17% ∓ 2.49% vs. 11.48% ∓ 1.11% ,P > 0.05; and effect-target cell ratio 20:1, 35.30% ∓ 3.78% vs. 17.19% ∓ 2.29%, P > 0.05).
CONCLUSIONNK cells transfected with DNTβR2 vector show better antitumor effect, which may provide new method for NK-based adoptive immunotherapy for cancer.
HT29 Cells ; Humans ; Killer Cells, Natural ; immunology ; metabolism ; Plasmids ; genetics ; Receptors, Transforming Growth Factor beta ; genetics ; Transfection ; Transforming Growth Factor beta ; metabolism ; pharmacology
5.Transforming Growth Factor-beta 1 Involved in the Pathogenesis of Endometriosis through Regulating Expression of Vascular Endothelial Growth Factor under Hypoxia.
Yue-Xin YU ; Yin-Ling XIU ; Xi CHEN ; Ya-Li LI
Chinese Medical Journal 2017;130(8):950-956
BACKGROUNDEndometriosis (EMs) is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. Transforming growth factor-beta 1 (TGF-β1) plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions.
METHODSEndometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA (mRNA) and protein expression levels of TGF-β1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) were measured. A Dual-Luciferase Reporter Assay was used to examine the effect of TGF-β1 and hypoxia on a VEGF promoter construct. Student's t-test was performed for comparison among groups (one-sided or two-sided) and a value of P < 0.05 was considered statistically significant.
RESULTSTGF-β1, VEGF, HIF-1α mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue (t = 2.16, P = 0.042). EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein (t = 6.84, P = 0.023). VEGF mRNA levels increased 12.5% in response to TGF-β, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production (87.5% increases) of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 (2.6-fold, t = 6.08, P = 0.032) or hypoxia (11.2-fold, t = 32.70, P < 0.001), whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect (18.5-fold, t = 33.50, P < 0.001).
CONCLUSIONSThe data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-β1 and hypoxia is taking place at the transcriptional level.
Blotting, Western ; Cells, Cultured ; Endometriosis ; genetics ; metabolism ; Female ; Humans ; Hypoxia ; genetics ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Transforming Growth Factor beta ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism
6.Comparison of TGF-beta1 expression of lung cancer in Gejiu miners with that in non-miners in other regions.
Ping JIANG ; Ke-wei JIN ; Qian GAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2004;22(1):36-38
OBJECTIVETo investigate the different expression of transforming growth factor beta(1) (TGF-beta(1)) in lung cancer specimens of Gejiu miners, and non-miners in other regions.
METHODSThirty specimens of Gejiu miners' lung cancer and 30 specimens of non-miners' were observed in this experiment. The expression of TGF-beta(1) protein and TGF-beta(1) mRNA were detected by the methods of immunohistochemistry and in situ hybridization. The results were quantitatively analyzed using image analysis system.
RESULTSThe positive rate of TGF-beta(1) protein expression in Gejiu miners and non-miners was 75.39%and 44.78% respectively, and the positive rate of TGF-beta(1) mRNA was 63.96% and 34.07% respectively. There were significant differences between the two groups (P < 0.01).
CONCLUSIONThe expression of TGF-beta(1) in lung cancer of Gejiu miners was significantly higher than that of non-miners. The pathogenesis of lung cancer may be different between Gejiu miner and non-miners. High expression of TGF-beta(1) may be one of the reasons of high incidence of lung cancer in Gejiu miners.
Humans ; Immunohistochemistry ; In Situ Hybridization ; Lung Neoplasms ; genetics ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Transforming Growth Factor beta ; genetics ; immunology ; Transforming Growth Factor beta1
7.Early expression of TGF-beta1, vimentin and desmin genes in renal cortex of diabetic rats.
Journal of Zhejiang University. Medical sciences 2004;33(1):55-59
OBJECTIVETo study the expression of TGF-beta(1)vimentin and desmin in the renal cortex of diabetic rats induced by STZ.
METHODSDiabetes was induced in 24 male SD rats by single intraperitoneal injection of 1.0%STZ (70 mg/kg). Twenty-four age, weight and sex matched SD rats were used as controls. The expression of TGF-beta(1),vimentin and desmin mRNA in the renal cortex were detected by RT-PCR on the 3rd, the 7th, the 14th and the 30th day after the DM rat model established.
RESULT(1)The expression of TGF-beta(1), vimentin mRNA in the renal cortex of diabetic rats gradually increased respectively from the 7th day and the 14th day after the model established, and the expressive intensity was significantly greater than that in controls (P<0.05 or P<0.01). However,the expression of desmin mRNA in the renal cortex of diabetic rats gradually decreased from the 14th day after the model established, and the expressive intensity was significantly less than that in controls (P<0. 05 or P<0.01). (2) The expression of TGF-beta(1)mRNA correlated positively to that of vimentin mRNA (r 0.740 P=0.000), while the expression of desmin mRNA correlated negatively to that of TGF-beta(1)mRNA (r 0.695 P=0.000) and to that of vimentin mRNA (r 0.591 P=0.002).
CONCLUSIONThe expression of renal cortical TGF-beta(1) and vimentin mRNA gradually increase while the expression of desmin mRNA gradually decrease during the first month of the diabetic model established suggest TGF-beta(1) may play a role in the transformation of renal tubular epithelial cells into fibroblast during the progressive interstitial fibrosis of diabetic nephropathy.
Animals ; Desmin ; genetics ; Diabetes Mellitus, Experimental ; metabolism ; Kidney Cortex ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Transforming Growth Factor beta ; genetics ; Transforming Growth Factor beta1 ; Vimentin ; genetics
8.Smad 7 and post-receptor signal regulation of transforming growth factor-beta1.
Jian-xin WU ; Xiang-jun MENG ; Yuan-wen CHEN ; Ji-lin CHENG ; Ding-guo LI ; Han-ming LU
Chinese Journal of Hepatology 2003;11(5):315-317
DNA-Binding Proteins
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chemistry
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genetics
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physiology
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Humans
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Liver Cirrhosis
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pathology
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physiopathology
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Receptors, Transforming Growth Factor beta
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physiology
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Signal Transduction
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physiology
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Smad7 Protein
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Trans-Activators
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chemistry
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genetics
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metabolism
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physiology
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Transcription, Genetic
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physiology
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Transforming Growth Factor beta
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physiology
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Transforming Growth Factor beta1
9.The significance of TGF-beta expression in scar in adenosine receptor A(2A) knockout mice.
Hu XIAO ; Li RAN ; Ying-ying ZHUO ; De-chang WANG ; Ran HUO ; Yi-bing WANG ; Yong-qiang FENG ; Qiang LI
Chinese Journal of Plastic Surgery 2010;26(2):136-138
OBJECTIVETo discuss the mechanism of scar hypertrophy in adenosine receptor A(2A) (A(2A) R) knockout mice.
METHODSAnimal models of hypertrophic scar were established in 12 A(2A) R knockout mice and 12 wild-type mice as control. The thickness and the size of transverse section of the hypertrophic scar were observed by H-E staining. The hydroxyproline (HYP) in the scar was measured colorimetrically. The TGF-beta expression was tested by Western blotting method.
RESULTSThe hypertrophic scar in wild-type mice was more severe than that in knockout mice. Compared with self-control, the increase of the thickness and the size of transverse section of hypertrophic scar was markedly higher in wild-type group than in the knockout group (P < 0.01). There was significant difference in HYP content between the two groups (P < 0.01). Compared with self-control, the increase of TGF-beta expression in wild-type group was much more than that in knockout group (P < 0.01).
CONCLUSIONSThe TGF-beta expression decreases in the A(2A) R knockout mice. The scar hypertrophy is also much less in the A(2A) R knockout mice.
Animals ; Cicatrix ; metabolism ; pathology ; Disease Models, Animal ; Mice ; Mice, Knockout ; Receptor, Adenosine A2A ; genetics ; Transforming Growth Factor beta ; genetics ; metabolism
10.Overexpression of TGF beta 1 increases elastin expression and adhesion of smooth muscle cells.
Chuhong ZHU ; Dajun YING ; Xinghong ZHU ; Jianhong MI ; Shiwu DONG ; Jian QIN
Journal of Biomedical Engineering 2003;20(4):597-600
This study was conducted to examine the effectiveness of a gene transfer of human TGF beta 1 gene into smooth muscle cells and whether the TGF beta 1 can increase elastin expression of smooth muscle cells. With the help of DOTAP, smooth muscle cells were transfected with pMAMneoTGF beta 1. The positive cell clones were selected with G418. The stable transfection and expression of TGF beta 1 in the smooth muscle cells were determined by immunofluorescence analysis. The expression of elastin in the transfected and untransfected cells were determined by in situ hybridization. The adhesion force between smooth muscle cells and matrix was detected by micropipette system. The results showed abundant TGF beta 1 stable expression in smooth muscle cells. TGF beta 1 gene can increase two-three times elastin expression and increase the adhesion between smooth muscle cells and matrix. TGF beta 1 can be used in vascular tissue engineering to increase smooth muscle cells adhesion.
Cell Adhesion
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Cells, Cultured
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Elastin
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biosynthesis
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Humans
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In Situ Hybridization
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Muscle, Smooth, Vascular
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cytology
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metabolism
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Transfection
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Transforming Growth Factor beta
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biosynthesis
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genetics
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physiology
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Transforming Growth Factor beta1