The transforming growth factor-β-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family. TAK1 plays important roles in many biological functions. Cardiac hypertrophy can be identified as physiological or pathological myocardial hypertrophy. TAK1 not only participates in the development of normal myocardium, but also plays an important role in regulating the occurrence and development of pathological myocardial hypertrophy. Angiotensin II (Ang II) or pressure overload induces pathological cardiac hypertrophy through different ways, such as hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional expression of TAK1, or transforming growth factor-β1 (TGF-β1)-, thyroid hormone-, ubiquitin protease-mediated TAK1 phosphorylation or ubiquitination. This article reviews the role of TAK1 in the occurrence and development of pathological myocardial hypertrophy and discusses the potential of TAK1 as an important target for the prevention and treatment of clinical myocardial hypertrophy.
Cardiomegaly ; Humans ; MAP Kinase Kinase Kinases ; genetics ; Myocardium ; Phosphorylation ; Transforming Growth Factor beta ; Transforming Growth Factor beta1

To conduct genetic analysis of pancreatic ductal adenocarcinoma tissues and analyze the correlation between targeted microRNA (miRNA) and pathways in pancreatic ductal adenocarcinoma.
 Methods: We collected 19 samples of peripheral venous blood serum from patients with pancreatic ductal adenocarcinoma in Hainan Provincial Hospital of Chinese Medicine, and also collected 21 blood serum samples as a control group of non-pancreatic ductal adenocarcinoma. We used the bioinformatics analysis of literature GCBI data platform for screening and analyzing the genetics of pancreatic ductal adenocarcinoma samples. Through GCBI data platform of hierarchy clustering analysis and the enrichment of gene function analysis, the relevant miRNA was screened as a research object in patients with pancreatic ductal adenocarcinoma. The miRNA was screened by literature analysis and pancreatic cancer gene analysis. Real-time PCR and Western blotting were carried out to study the relationship between the selected miRNA and TGF-β1 by overexpression and suppression of the gene in pancreatic ductal adenocarcinoma cells.
 Results: MiRNA-21 was screened as a gene associated with pancreatic ductal carcinoma via hierarchy clustering analysis and gene function analysis. MiRNA-21 was highly expressed in the pancreatic ductal carcinoma patients. Expressions of TGF-β1 were inhibired in miRNA-21 overexpressed PANC-1. While the expression of miRNA-21 was inhibited, TGF-β1 expression increased obviously.
 Conclusion: MiRNA-21 is highly expressed in patients with pancreatic ductal adenocarcinoma, can regulate the expression of TGF-β1, which may be a mechanism of miRNA-21 in pancreatic ductal adenocarcinoma.
Carcinoma, Pancreatic Ductal ; genetics ; Humans ; MicroRNAs ; genetics ; Pancreatic Neoplasms ; genetics ; Transforming Growth Factor beta1

Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix (ECM). Transforming growth factor-beta (TGF-Β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference (RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA (siRNA) targeting TGF-Β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-Β1 siRNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-Β1 and TGF-Β1 siRNA in liver fibrosis.
Liver Cirrhosis ; therapy ; RNA, Small Interfering ; genetics ; Transforming Growth Factor beta1 ; genetics

OBJECTIVETo analyze the polymorphism at -509C/T site of TGF-β1 gene in patients with keloids, and to explore its relationship with the occurrence of keloid and its influence on the plasma level of TGF-β1.

METHODSOne hundred and sixty-nine patients with keloids and hospitalized from June 2011 to April 2014 were included as keloid group, and 119 healthy blood donors were enrolled as healthy control group. Venous blood of study subjects was collected. The -509C/T genotype of TGF-β1 gene was determined with PCR-restriction fragment length polymorphism technique combined with DNA sequence analysis, and the frequency of allele C or T was calculated. The theoretical frequency of the 3 genotypes CC, CT, and TT was calculated according to the theory of Hardy-Weinberg equilibrium to determine whether the gene frequency of the study subject was group representative or not. The distribution of -509C/T genotype of TGF-β1 gene among patients in keloid group was analyzed by grouping in gender, age, with or without family history of keloid, and the number of keloid respectively. Plasma level of TGF-β1 of all study subjects was determined with ELISA, and the plasma level TGF-β1 of patients with various -509C/T genotypes of TGF-β1 gene in keloid group was analyzed. The relative risk of allele frequency of patients in keloid group was analyzed by Logistic regression analysis, and the other data were processed with chi-square test and t test.

RESULTSAmong the -509C/T genotypes of TGF-β1 gene between subjects in the two groups, the distribution of genotypes CC, CT, and TT was quite similar, and they were respectively 38 cases (22.5%), 79 cases (46.7%), and 52 cases (30.8%) in keloid group and 39 persons (32.8%), 52 persons (43.7%), and 28 persons (23.5%) in healthy control group (χ² = 4.225, P>0.05). The distribution frequency of alleles C and T in the two groups were obviously different, and they were respectively 45.9% and 54.1% in keloid group and 54.6% and 45.4% in healthy control group (χ² = 4.291, P<0.05). The theoretical frequency values of the three kinds of genotypes of CC, CT, and TT were respectively 35 cases (21.0%), 84 cases (49.7%), and 50 cases (29.3%) in keloid group, and 35 persons (29.8%), 59 persons (49.6%), and 25 persons (20.6%) in healthy control group. There were no statistically significant differences between the actual genotype frequency and the theoretical values (with χ² values respectively 0.581 and 1.672, P values above 0.05), showing that the research group reached Hardy-Weinberg equilibrium. Relative risk analysis of allele frequency showed that the risk of suffering from keloid of patients carrying allele C was 1.421 times of that of patients without carrying allele C (odds ratio = 1.421, with 95% confidence interval 1.109-1.983, P < 0.05). The distribution of -509C/T genotypes of TGF-β1 gene among patients in keloid group was similar by grouping in gender, age, and number of keloid (with χ² values 0.895-5.008, P values above 0.05). Between patients with or without family history of keloid, the differences of distribution frequencies of genotypes CC and CT were significantly different, which were respectively 61.8% (21/34) and 37.8% (51/135) in patients with family history of keloid and 14.7% (5/34) and 34.1% (46/135) in patients without a family history of keloid, with χ² values respectively 6.391 and 4.835, P values below 0.05; the distribution frequency of genotype TT was close (χ² = 0.292, P > 0.05). The plasma level of TGF-β1 of patients in keloid group was (42 ± 9) µg/L, which was significantly higher than that of people in healthy control group \[(34 ± 8) µg/L, t = 4.408, P < 0.05\]. In keloid group, the plasma level of TGF-β1 in patients with genotype CC and that of patients with genotype CT was quite similar, which were respectively (43 ± 9) and (40 ± 9) µg/L (t = 0.680, P > 0.05), and they were significantly higher than that of patients with genotype TT \[(34 ± 8) µg/L, with t values respectively 2.676 and 2.137, P values below 0.05\].

CONCLUSIONSTGF-β1 gene -509C/T polymorphism was shown to be present in patients with keloids who were admitted to our hospital. It was shown to influence the plasma level of TGF-β1 in patients. The individuals who carry TGF-β1 allele C may increase the risk of developing keloid by promoting the expression of TGF-β1.

Alleles ; Gene Frequency ; Genotype ; Humans ; Keloid ; genetics ; Polymorphism, Genetic ; Transforming Growth Factor beta1 ; blood ; genetics

BACKGROUNDMutations in the transforming growth factor beta I (TGFBI) gene cause several types of autosomal-dominant corneal dystrophies. We investigated the role of this gene in a Chinese family affected by granular corneal dystrophy (GCD).

METHODSFamily history and phenotypic data were recorded. The diagnosis of GCD was made on the basis of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intron-exon boundary sequences of TGFbetaI were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing.

RESULTSA heterozygous C to T transition at nucleotide c.1663 (CGG to TGG R555W) of TGFbetaI gene was present in two affected members but was absent in the rest of the family members.

CONCLUSIONA recurrent pathogenic R555W of TGFbetaI gene mutation is identified, which appears to be the predominant mutations causing GCD in different populations.

Adult ; Corneal Dystrophies, Hereditary ; genetics ; Female ; Humans ; Middle Aged ; Mutation ; Transforming Growth Factor beta1 ; genetics

OBJECTIVETo explore the mechanism of moxibustion arresting the pulmonary fibrosis and provide experimental basis for prevention and treatment of pulmonary fibrosis with acupuncture and moxibustion.

METHODSOne hundred and forty SD rats were randomly assigned to 4 groups: a blank group, a model group, a moxibustion group and a prednisone group, 35 rats in each group. The 3 groups expect the blank group were injected with bleomycin via trachea to induce experimental pulmonary fibrosis model, and 7 days after modeling, they were treated with moxibustion at bilateral Feishu (BL 13) and Gaohuang (BL 43), 3 cones each point, once each day, 10 days constituting one therapeutic course with an interval of one day between courses. After 3 courses, all rats were killed and expressions of TGF-beta1mRNA were detected with PCR method.

RESULTSThe content of TGF-beta1mRNA in the pulmonary tissue in the moxibustion group and the prednisone group was significantly lower than the model group (P < 0.01), and there was no significant difference between the moxibustion group and the prednisone group (P > 0. 05).

CONCLUSIONBoth moxibustion at Feishu (BL 13) and Gaohuang (BL 43), and prednisone treatment can significantly suppress the expression of TGF-beta1mRNA in the pulmonary tissue in the rat of bleomycin-induced pulmonary fibrosis.

Animals ; Bleomycin ; Humans ; Moxibustion ; Pulmonary Fibrosis ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; genetics

OBJECTIVE: To investigate high-salt exposure-induced polarization of mononuclear macrophages and the changes in proliferation and phenotypic transformation of renal fibroblasts in a co-culture system. METHODS: Cultured mononuclear macrophages were exposed to high salt (161 mmol/L Na +) for 2 h and the surface markers of M0, M1 and M2-type macrophages were detected with RT-qPCR. The culture medium of the macrophages in normal and high-salt groups was collected for detection of the mRNA and protein levels of IL-6 and TGF-β1 using RT-qPCR and ELISA. A co-culture system of high salt-exposed macrophages and renal fibroblasts (NRK-49F) was established using a Transwell chamber, and the changes in proliferation and migration of NRK-49F cells were examined using EdU assay and Transwell assay, respectively. Western blotting was performed to detect the expressions of collagen I, collagen III and collagen α-SMA in NRK-49F cells. RESULTS: The high salt-exposed macrophages showed significantly increased mRNA levels of M2-type macrophage surface markers mannose receptor and arginase ( CONCLUSIONS High-salt exposure induces polarization of mononuclear macrophages into M2-type macrophages and promotes secretion of IL-6 and TGF-β1 by the macrophages to induce the proliferation and phenotypic transformation of NRK-49F cells.
Cell Proliferation ; Coculture Techniques ; Fibroblasts ; Kidney ; Macrophages ; Transforming Growth Factor beta1/genetics*

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

Animals ; Cell Line ; Collagen Type I ; biosynthesis ; Hepatic Stellate Cells ; metabolism ; RNA, Messenger ; genetics ; Rats ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Transforming Growth Factor beta3 ; genetics ; metabolism

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