Objective To explore whether the polymorphism of transforming growth factor β1 (TGF β1) gene at 869T/C and 915G/C loci contributes to the genetic susceptibility to hypertension. Methods Assessed under the same criteria, all case control studies on relationship between the polymorphism of TGF β1 gene and hypertension were searched in both English and Chinese databases. All articles retrieved were screened and evaluated, and meta-analyses were conducted with RevMan 5.1 software. Results A total of 14 case control studies were included. The results of meta-analyses showed TGF β1 gene C allele was related to hypertension (OR=1.37, 95%CI 1.21 to 1.54). It was noted that individuals with CC genotype and TT genotype had a significant increased risk of hypertension (OR=1.43, 95%CI 1.27 to 1.60; OR=0.64, 95%CI 0.53 to 0.78, respectively). And there was no b evidence showing that TGF β1 915G/C genetic polymorphism was related to hypertension. The results from meta-analyses of the studies based on Chinese population on the two loci were in consistent with the outcomes of overall meta-analyses. Sensitivity analyses indicated the results were stable. And publication bias was not present, reflected by P values from Egger’s regression asymmetry test and Begg’s adjusted rank correction test. Conclusions 869T/C polymorphism of TGF β1 gene is associated with hypertension. C allele is potentially one of the genetic risk factors for hypertension. Present studies do not support a direct relationship between 915G/C polymorphism TGF β1 gene and hypertension.
目的：研究转化生长因子β1（TGF-β1）促进Tenon囊成纤维细胞的增殖作用及核心蛋白多糖（decorin）对TGF-β1促Tenon囊成纤维细胞增殖的影响。方法：（1）取青光眼患者的Tenon囊组织，采用组织块贴壁培养法进行原代培养细胞培养，细胞经过冷冻与复苏后，观察细胞形态结构与生物学特性。（2）用不同浓度(0.01、0.1、1、5、10ng/mL)TGF-β1作用于Tenon囊成纤维细胞48 h。（3）终浓度为5 ng/mL的TGF-β1 和不同浓度(0.01、0.1、1、2、5μg/mL)的decorin共同作用于Tenon囊成纤维细胞48h。MTT比色法检测Tenon囊成纤维细胞增殖。结果：（1）体外成功培养Tenon囊成纤维细胞，细胞生长活跃，形状稳定，细胞经过冷冻与复苏后，仍能保持其原来的细胞形态结构与稳定的生物学特性。（2）1～10ng/mL TGF-β1能促进Tenon囊成纤维细胞的增殖，并与浓度成正比。（3）2～5μg/mL decorin 能抑制TGF-β1促Tenon囊成纤维细胞增殖作用，其抑制作用与浓度成正比。结论： TGF-β1可刺激Tenon囊成纤维细胞增殖，Decorin能抑制TGF-β1促进细胞增殖的作用，其机理可能通过与TGF-β1结合抑制青光眼滤过手术后瘢痕形成。
ObjectiveTo explore the expressions of prostaglandin F2α receptor (PTGFR) and cyclooxygenase-2 (COX-2) in tissues of benign bile duct scar and their significances, and investigate the regulating effect of transforming growth factor-β1 (TGF-β1) on the expression of PTGFR in human bile duct fibroblasts cultured in vitro. MethodsThe samples of common bile duct (CBD) scars were collected from 18 patients with benign bile duct scar stricture and 6 cases of normal CBD tissues from liver transplantation donor were collected as control. The expressions of PTGFR and COX-2 were detected by immunohistochemical strept-avidin-biotin complex (SABC) method. Semiquantitative RT-PCR and ELISA methods were used to detect the mRNA and protein levels of PTGFR in bile duct fibroblasts which were effected by TGF-β1 with different concentrations (0, 10, 20, and 30 ng/ml) for 24 h. ResultsThe positive rates of PTGFR and COX-2 were 88.9% (16/18) and 83.3% (15/18) in tissues of benigh CBD scar and 33.3% (2/6) and 0 (0/6) in normal CBD tissues (Plt;0.05). The expressions of the PTGFR mRNA and protein levels became upregulated when the concentrations of the TGF-β1 became higher in human bile duct fibroblasts (Plt;0.05). And the effect was concentration dependant to some extent. ConclusionsThe high expressions of PTGFR and COX-2 play important roles in the process of benign bile duct stricture formation. TGF-β1 is able to induce higher expressions of PTGFR mRNA level and the PTGFR protein level in a concentration dependent manner, and regulate the formation of benign bile duct stricture.
【Abstract】ObjectiveTo detect p27 expression in rectal carcinoma and serum transforming growth factor-β1 (TGF-β1) level in these patients, and to elucidate the modulatory effect of serum TGF-β1 on p27 expression in rectal carcinoma. MethodsExpression of p27 was measured in 37 cases of rectal carcinoma, 22 of rectal adenoma and 19 of normal control specimens by immunohistochemical staining using antibodies to p27. Serum level of TGFβ1 was measured in these patients by enzymelinked immunosorbent assay (ELISA) method. Resultsp27 protein was expressed in normal rectal tissue, rectal adenoma and rectal carcinoma, and the positive rate was 89.47%, 90.91% and 64.87%, respectively. The positive rate of p27 in rectal carcinoma was significantly lower than that of normal rectal tissue and rectal adenoma (P=0.025). p27 was mainly located in nucleolus of normal rectal tissue and rectal adenoma, and the positive rate of p27 in cytoplasm of rectal carcinoma was higher than that of normal and rectal adenoma. The positives rates of serum TGF-β1 in normal group, rectal adenoma group and rectal carcinoma group were 21.05%, 27.27% and 51.35%(P=0.045),respectively. The expression of p27 related to histological differentiation, lymph node metastasis and infiltration depth. Serum level of TGF-β1 related to lymph node metastasis, infiltrated depth and CEA level. The positive rate of p27 in TGF-β1 negative group and positive group was 88.89% and 42.11%(MantelHaenszel χ2=6.755,P=0.009), respectively. ConclusionTGF-β1 may be useful in assessment of malignance and prognosis of rectal carcinoma. TGF-β1 can downregulate p27 expression in rectal carcinoma.
【Abstract】Objective To investigate the expression of tumor growth tactor β1 (TGFβ1) and p27 in gallbladder carcinoma and their relation to the development of the carcinoma. Methods The expression of TGF-β1 and p27 in 36 cases of gallbladder carcinoma was detected by SP immunohistochemical staining. Twenty cases of chronic cholecystitis were collected as control. Results The positive rate of TGF-β1 （63.9%） was higher than that of the control （10.0%），P＜0.05， and the positive rate of p27 (47.2%) was lower than that of the control 100%(P＜0.05). The positive rate of TGF-β1 was significantly higher in metastasis or Nevin Ⅳ～Ⅴ stage cases than that of non-metastasis or Nevin Ⅰ～Ⅲ stage cases 33.3% (P＜0.05). The positive rate of p27 was statistically higher in moderate and highly differentiation (60.9%), nonmetastasis (75.0%) or Nevin’s Ⅰ～Ⅲ stage (75.0%) cases than those of poor differentiation (23.0%), metastasis (33.3%) and Nevin Ⅳ～Ⅴ stage (33.3%) cases (P＜0.05). The expression of p27 was negatively correlated with that of TGF-β1(r=-0.4473，P＜0.05). There was significant difference in survival time between patients with TGF-β1 positive and TGF-β1 negative（P＜0.05）. The difference was also found between patients with p27 positive and p27 negative. Conclusion The upregulation of TGF-β1 and downregulation of p27 in gallbladder carcinoma indicates the imbalance of TGF-β1/p27 system, which may play a role in the carcinogenesis and predict the malignant behaviors of the carcinoma.
ObjectiveTo introduce transforming growth factor β(TGFβ) and the relationship between TGFβ and graft rejection. Methods Relevent articles in recent years were reviewed.ResultsThe immunodepressive function of TGFβ could resist transplant organ rejection injury in early postoperative period ; meanwhile TGFβ also caused fibroblast migration and promoted matrix deposition by increasing collagen production and decreasing collagen breakdown via inhibition of collagenases,which resulted in transplant organ fibrosis and arteriosclerosis, gene polymorphisms of the TGFβ were associated with it. Moreover,ischemia reperfusion injury and immunodepressive drug also affected production of TGFβ.ConclusionTGFβ as a pleiotropic and multifunctional cytokine contributes to the development of acute and chronic rejection.
The expressions and significance of c-met oncoprotein and transforming growth factor-α (TGF-α) were studied by immunohistochemical method in 50 cases of breast cancer (BC) and 12 cases of benign lesions of breast (BL). The positive rate of c-met, TGF-α in BC was 26.0% and 25.0% respectively, in BL was 8.3% and 25.0% respectively. The positive rate of c-met oncoprotein was lower in the cases of histologic Grade Ⅰ, positive of ER and PR or CEA than that of histologic Grade Ⅲ, negative of ER and PR or CEA. The positive rate of TGF-α was lower in the cases of histologic Grade Ⅰ, negative of ER and PR or CEA than that of histologic Grade Ⅲ, positive of ER and PR or CEA. These results suggest the expression of c-met and TGF-α might be related to the carcinogenesis and development or endocrine state of BC.
Objective To investigate the effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in rats with pulmonary fibrosis，and explore the mechanism of sodium ferulate on pulmonary fibrosis.Methods A rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin (5 mg/kg).Thirty SD rats were randomly divided into three groups (n=10 in each group)，ie.a control group，a pulmonary fibrosis model group，and a sodium ferulate group.The lung histopathology and the expression of collagen was examined by HE staining and collagen fibril staining respectively.The expressions of TGF-βRII and Smad4 mRNA in the lung tissue were detected by situ hybridization.And the expression of TGF-β1 mRNA was detected by real-time fluorescence-quantification RT-PCR.Results Collagen fibril staining indicated that the expression of pulmonary collagen in the model group was significantly higher than that in the control group and sodium ferulate group (Plt;0.001).The mRNA expressions of pulmonary TGF-β1，TGF-βRII and Smad4 were significantly higher in the model group than those in the control group (all Plt;0.01)，and were significantly lower in the sodium ferulate group than those in the model group (all Plt;0.05).Conclusions Sodium ferulate can effectively reduce pulmonary fibrosis through inhibition of the mRNA expression of TGF-β1，TGF-βRII and Smad4 in the lung tissue，thus influence the TGF-β1/Smad4 signal transduction way and inhibit the target gene activation.
Objective To investigate the role of IFN-γ in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods Seventy-five SD rats were randomly divided into five groups (15 rats in each group)，ie.a normal group，a bleomycin-induced pulmonary fibrosis model group，a dexamethasone-treated group，a high-dose IFN-γ-treated group (150 000 U/kg) and a low-dose IFN-γ-treated group (50 000 U/kg).Five rats in each group were randomly killed in 7th day，14th day and 28th day after relative treatment respectively，and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical method were adapted to determine protein levels of TGF-β1，CTGF，type Ⅰcollagen and type Ⅲ collagen in pulmonary tissues.Results Histopathological study showed that treatment with either dexamethasone or IFN-γ (both high dose and low dose) remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis (compared with model group，all Plt;0.05).Histoimmunochemical study suggested that both dexamethasone and IFN-γ could inhibit the expression of TGF-β1，CTGF，type Ⅰand type Ⅲ collagen (compared with model group，all Plt;0.05)，and the suppression of TGF-β1，type Ⅰand type Ⅲ collagen expression was more obvious in high-dose IFN-γ-treated group than those in low-dose group (Plt;0.05).Conclusions INF-γ possesses apparent anti-fibrosis effect that is similar to dexamethasone but with less side effect.Such effect may resulted from reduced production of type Ⅰand type Ⅲ collagen through expression inhibition of cytokines such as TGF-β1 and CTGF.
Objective To study the inhibitory effects of curcumin on bleomycin-induced pulmonary fibrosis in rats at the fibrosing stage and explore its possible mechanism.Methods 96 male SD rats were randomly divided into a normal control group，a fibrosis model group，a fibrosis model treated with prednisone group and a fibrosis model treated with curcumin group.Pulmonary fibrosis were induced by instilled bleomycin through tracheal.From day 15 after bleomycin administration，the curcumin group and prednisone group were given curcumin（300 mg/kg） or prednisone（5 mg/kg） per day by intragastric administration，respectively.The normal control group and fibrosis model group were given 1% sodium carboxymethyl cellulose（10 mL/kg） as control.Six rats of each group were randomly sacrificed on day 21，28，42 and 56 after bleomycin administration，respectively.The histological changes of the lung were evaluated by HE and Masson’s trichrome staining.Lung expressions of transforming growth factor-β1（TGF-β1） and hydroxyproline were assessed by immuno-histochemistry and digestion method，respectively.Results Pulmonary fibrosis and hydroxyproline level in the curcumin group were significantly reduced as compared with those in the model group on day 42 and 56.The expession of TGF-β1 in the curcumin group was significantly lower than that in the model group on day 28，42 and 56，and was not significantly different from the normal group on day 56.Conclusion Curcumin could alleviate bleomycin-induced pulmonary fibrosis in rats at the fibrosing stage by inhibiting the expressions of TGF-β1.