OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

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

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

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 ; Human ; Male ; Middle Age ; Prognosis ; RNA, Messenger/genetics/metabolism ; Receptors, Transforming Growth Factor beta/*genetics ; Stomach Neoplasms/*genetics/metabolism ; Transforming Growth Factor beta/metabolism

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

Animals ; Heparin ; pharmacology ; Hepatocytes ; cytology ; metabolism ; Mice ; Promoter Regions, Genetic ; genetics ; Transforming Growth Factor beta ; genetics

Humans ; Polymorphism, Genetic ; Pulmonary Fibrosis ; genetics ; physiopathology ; Transforming Growth Factor beta ; genetics ; physiology

DNA-Binding Proteins ; chemistry ; genetics ; physiology ; Humans ; Liver Cirrhosis ; pathology ; physiopathology ; Receptors, Transforming Growth Factor beta ; physiology ; Signal Transduction ; physiology ; Smad7 Protein ; Trans-Activators ; chemistry ; genetics ; metabolism ; physiology ; Transcription, Genetic ; physiology ; Transforming Growth Factor beta ; physiology ; Transforming Growth Factor beta1

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

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