Dataset Information

Transforming Growth Factor- ? 1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study.

ABSTRACT: The interindividual variations in the capacity of transforming growth factor- ? 1 (TGF- ? 1) production have been ascribed to genetic polymorphisms in TGF- ? 1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF- ? 1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF- ? 1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher (P < 0.05) in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (P < 0.01). TGF- ? 1 was significantly (r = -0.684; P < 0.001) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF- ? 1 gene (T29C) in HBV infection.

SUBMITTER: Talaat RM

PROVIDER: S-EPMC3878635 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transforming Growth Factor- β 1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study.

Talaat Roba M RM Dondeti Mahmoud F MF El-Shenawy Soha Z SZ Khamiss Omaima A OA

Hepatitis research and treatment 20131218

The interindividual variations in the capacity of transforming growth factor- β 1 (TGF- β 1) production have been ascribed to genetic polymorphisms in TGF- β 1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF- β 1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. ...[more]

PMID: 24455227

Similar Datasets

Project description:UnlabelledHepatitis B virus (HBV) infection causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). Previously, we found that HBV mRNAs can absorb microRNA-15a (miR-15a) to affect apoptosis through the Bcl-2 pathway. We asked whether HBV could inhibit apoptosis and promote tumorigenesis through different pathways. In this study, we found that the transforming growth factor β (TGF-β) pathway-inhibitory factor Smad7 is a novel target of miR-15a. We demonstrated that HBV can upregulate the level of Smad7 by downregulating miR-15a. Furthermore, we examined the level of Smad7 in liver samples from HBV-infected HCC patients and found that HBV mRNAs are positively correlated with the level of Smad7. By taking the approach of using immunoblotting and luciferase reporter assays, we revealed that HBV can abrogate TGF-β signaling via upregulating Smad7. By using annexin V staining and caspase 3/7 activity assays, we found that HBV can inhibit TGF-β-induced apoptosis of HepG2 cells. We also showed that HBV can promote tumor growth in BALB/c nude mice through upregulating the expression of Smad7. In conclusion, we demonstrated that HBV can upregulate Smad7 expression and inhibit TGF-β signaling, which makes the cells resistant to TGF-β-induced apoptosis and promotes tumorigenesis.ImportanceHepatitis B virus (HBV) infection causes chronic hepatitis, which can eventually lead to hepatocellular carcinoma (HCC). TGF-β signaling is closely linked to liver fibrosis, cirrhosis, and subsequent HCC progression and plays a unique role in the pathogenesis of HCC. At the early stage of tumor formation, TGF-β functions as a tumor suppressor that inhibits cell proliferation and induces apoptosis. Previously, we found that HBV mRNAs can sponge off miR-15a to affect apoptosis through the Bcl-2 pathway. In this study, we identified that the TGF-β-inhibitory factor Smad7 is a novel target of miR-15a. We reveal that HBV can abrogate TGF-β signaling via upregulating Smad7, inhibit TGF-β-induced apoptosis, as well as promote tumor development. Our study provides evidence to support the idea that viral RNAs can exert their functions as competing endogenous RNAs (ceRNAs) toward microRNA and participate in important cellular processes.

Project description:ObjectiveTo explore the association between transforming growth factor-beta1 (TGF-?1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.MethodsSystematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg's funnel plot and Egger's test.ResultsA total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-?1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR?=?1.08,95%CI?=?0.88-1.32; CC vs. TT:OR?=?1.17,95%CI?=?0.79-1.72; CT vs. TT: OR?=?0.91, 95%CI?=?0.68-1.22; CC+CT vs. TT: OR?=?0.99, 95%CI?=?0.73-1.35; CC vs. CT+TT: OR?=?1.23, 95%CI?=?0.95-1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR?=?1.18, 95%CI?=?1.05-1.32; CC vs. TT: OR?=?1.40, 95%CI?=?1.10-1.77; CT vs. TT: OR?=?1.23, 95%CI?=?1.02-1.49; CC+CT vs. TT: OR?=?1.27, 95%CI?=?1.03-1.57; CC vs. CT+TT, OR?=?1.21, 95%CI?=?0.99-1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR?=?0.72, 95%CI?=?0.57-0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.ConclusionThis meta-analysis suggested that current epidemiological studies of TGF-?1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.

Project description:BackgroundNerve growth factor (NGF) contributes to pain in knee osteoarthritis (KOA) patients. Transforming growth factor-beta (TGF-β) stimulates NGF expression in chondrocytes from KOA patients. However, the correlation between synovial TGF-β and NGF levels has not been sufficiently studied in human KOA patients. Further, the mechanism governing NGF regulation by TGF-β in synovial cells is unclear.MethodsDuring total knee arthroplasty, we extracted the synovial tissue (SYT) of 107 subjects with unilateral Kellgren/Lawrence grade 3-4 KOA confirmed by radiography. We examined the distribution of TGF-β and NGF using immunohistochemistry, and analyzed the relationship between NGF and TGFB mRNA levels. Cultured synovial cells extracted from SYT were exposed to culture medium (control), human recombinant TGF-β (rhTGF-β), rhTGF-β + ALK5 inhibitor SB505124, rhTGF-β + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or rhTGF-β + p38 inhibitor SB203580 for 30 min, 6 h and 24 h. NGF mRNA expressed by the cultured cells and NGF protein levels in the cell supernatant were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of p38 was evaluated by western blotting.ResultsNGF mRNA levels were positively correlated with those of TGFB. Cells expressing TGF-β and NGF protein were observed in the lining layer of SYT. TGF-β stimulated increased NGF mRNA expression and NGF protein production. The ALK5 inhibitor completely suppressed the TGF-β-mediated increase in NGF expression and NGF production in synovial cells. ALK5, TAK1 and p38 inhibitors inhibited the TGF-β-induced phosphorylation of p38, and TAK1 and p38 inhibitors partially inhibited the TGF-β-mediated increase in NGF expression and NGF production in synovial cells.ConclusionTGF-β regulates NGF production via the TGF-β/ALK5 signaling pathway in osteoarthritic synovium. This effect may partially occur through inhibition of the TAK1/p38 pathway in the SYT of KOA patients.

Dataset Information

Transforming Growth Factor- ? 1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study.

Publications

Transforming Growth Factor- β 1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets