Dataset Information

Transforming growth factor-? signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

ABSTRACT: The transforming growth factor-? (TGF-?) signaling pathway and its relevant genes have been correlated with an increased risk of developing various hallmarks of metabolic syndrome (MetS). In this study, we assessed whether the TGF-? signaling pathway-associated genes of SMAD family member 2 (SMAD2), SMAD3, SMAD4, transforming growth factor beta 1 (TGFB1), TGFB2, TGFB3, transforming growth factor beta receptor 1 (TGFBR1), and TGFBR2 are associated with MetS and its individual components independently, through complex interactions, or both in a Taiwanese population. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our results showed a significant association of MetS with the two single nucleotide polymorphisms (SNPs) of SMAD2 rs11082639 and TGFBR2 rs3773651. The association of MetS with these SNPs remained significant after performing Bonferroni correction. Moreover, we identified the effect of SMAD2 rs11082639 on high waist circumference. We also found that an interaction between the SMAD2 rs11082639 and TGFBR2 rs3773651 SNPs influenced MetS. Our findings indicated that the TGF-? signaling pathway-associated genes of SMAD2 and TGFBR2 may contribute to the risk of MetS independently and through gene-gene interactions.

SUBMITTER: Lin E

PROVIDER: S-EPMC5648797 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Transforming growth factor-β signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

Lin Eugene E Kuo Po-Hsiu PH Liu Yu-Li YL Yang Albert C AC Tsai Shih-Jen SJ

Scientific reports 20171019 1

The transforming growth factor-β (TGF-β) signaling pathway and its relevant genes have been correlated with an increased risk of developing various hallmarks of metabolic syndrome (MetS). In this study, we assessed whether the TGF-β signaling pathway-associated genes of SMAD family member 2 (SMAD2), SMAD3, SMAD4, transforming growth factor beta 1 (TGFB1), TGFB2, TGFB3, transforming growth factor beta receptor 1 (TGFBR1), and TGFBR2 are associated with MetS and its individual components independe ...[more]

PMID: 29051557

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Project description:Skeletal malocclusions are common phenotypes in humans and have a strong influence on genetic factors. Transforming growth factor beta (TGFβ) controls numerous functions of the human body, including cell proliferation, differentiation, and migration. Thus, this study is aimed at evaluating whether genetic polymorphisms in TGFB1 and its receptor TGFBR2 are associated with mandibular retrognathism in German children and adolescents. Children and teenagers older than 8 years in the mixed or permanent dentition were included in this study. Patients with syndromes and facial trauma and patients with congenital alterations were excluded. Digital cephalometric tracings were performed using the anatomical landmarks point A, point B, sella (S), and nasion (N). Patients that have a retrognathic mandible (SNB < 78°) were selected as case group, and the patients with an orthognathic mandible (SNB = 78°- 82°) were selected as the control group. Genomic deoxyribonucleic acid (DNA) from saliva was used to evaluate four genetic polymorphisms in TGFB1 (rs1800469 and rs4803455) and TGBR2 (rs3087465 and rs764522) using real-time PCR. Chi-square or Fisher exact tests were used to compare gender, genotype, and allele distribution among groups. Genotype distribution was calculated in an additive and recessive model. Haplotype analysis was also performed. The established alpha of this study was 5%. A total of 146 patients (age ranging from 8 to 18 years) were included in this epidemiological genetic study. The genetic polymorphism rs3087465 in TGFBR2 was associated with mandibular retrognathism. Carrying the AA genotype in the rs3087465 polymorphism decreased the chance of having mandibular retrognathism (odds ratio = 0.25, confidence interval 95% = 0.06 to 0.94, p = 0.045). None of the haplotypes was associated with mandibular retrognathism (p > 0.05). In conclusion, we found that the genetic polymorphism rs3087465 in the promoter region of the TGFBR2 was associated with mandibular retrognathism in Germans.

Project description:BackgroundIntegrin alpha 2 (ITGA2) has been recently reported to be an oncogene and to play crucial roles in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study showed that ITGA2 was overexpressed in pancreatic cancer and promoted its progression. However, the mechanism of ITGA2 overexpression and other mechanisms for promoting the progression of pancreatic cancer are still unclear.MethodsThe GEPIA database was used to confirm the expression of ITGA2 in pancreatic cancer. To verify the influence of ITGA2 and TGF-β on the morphological changes of pancreatic cancer and tumor cell progression, we conduct CCK8 test, plate cloning, flow cytometry experiments and animal experiments. Then we conduct Western blot, RT-qPCR to explore the relationship between ITGA2 and TGF-β, and then find the key molecules which can regulate them by immunoprecipitation, Western blot, RT-qPCR, CHIP, nuclear and cytoplasmic separation test.ResultsThe results of the present study show that the abnormal activation of KRAS induced the overexpression of ITGA2 in pancreatic cancer. Moreover, ITGA2 expression significantly suppressed the activation of the TGF-β pathway. ITGA2 silencing enhanced the anti-pancreatic cancer proliferation and tumor growth effects of TGF-β. Mechanistically, ITGA2 expression suppressed the activation of the TGF-β pathway by inhibiting the SMAD2 expression transcriptionally. In addition, it interacted with and inhibited the nuclear translocation of TFCP2, which induced the SMAD2 expression as a transcription factor. Furthermore, TFCP2 also induced ITGA2 expression as a transcription factor, and the TFCP2 feedback regulated the ITGA2-TFCP2-SMAD2 pathway.ConclusionsTaken together, these results indicated that ITGA2 expression could inhibit the activation of the TGF-β signaling pathway in pancreatic cancer via the TFCP2-SMAD2 axis. Therefore, ITGA2, by effectively enhancing the anti-cancer effects of TGF- β, might be a potential clinical therapeutic target for pancreatic cancer.

Dataset Information

Transforming growth factor-? signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

Publications

Transforming growth factor-β signaling pathway-associated genes SMAD2 and TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.

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