ABSTRACT
Angiotensin II type 1 receptor (AT1R) antibodies directly injure endothelial and vascular smooth muscle cells by activating transcription factors associated with proinflammatory responses. Previous studies have shown that AT1R antibodies are associated with allograft rejection and decreased graft survival in kidney transplantation. Development of enzyme-linked immunosorbent assay has facilitated semiquantitative detection of AT1R antibodies. Assessing AT1R antibodies along with donor specific human leukocyte antigen antibodies may have potential to identify patients with possible risk for allograft injury and improve overall outcomes. In this review, we summarize recent clinical studies about AT1R antibodies in kidney transplantation and provide perspectives for future research area.
Subject(s)
Humans , Activating Transcription Factors , Allografts , Angiotensin II , Angiotensins , Antibodies , Enzyme-Linked Immunosorbent Assay , Graft Survival , Kidney Transplantation , Kidney , Leukocytes , Muscle, Smooth, Vascular , Receptor, Angiotensin, Type 1 , Tissue Donors , TransplantationABSTRACT
<p><b>OBJECTIVE</b>To explore the intervention of baicalin on signal transduction and activating transcription factor expression of ulcerative colitis (UC) patients.</p><p><b>METHODS</b>Recruited were UC patients at Outpatient Department of Digestive Disease, Inpatient Department of Digestive Disease, Center for Digestive Endoscopy of College City Branch, Guangdong Provincial Hospital of Traditional Chinese Medicine, and Southern Hospital affiliated to Southern Medical University from June 2010 to January 2011. They were assigned to the UC group (33 cases) and the diarrhea-predominant irritable bowel syndrome (IBS-D) group (30 cases). Another 30 healthy subjects were recruited as a healthy control group. Peripheral blood mononuclear cells (PBMCs) in vitro intervened by different concentrations baicalin were taken from UC patients. IL23R gene expressions in vitro intervened by different concentrations baicalin were detected using Q-PCR. Expressions of signal transducer and activator of transcription 4 (STAT4) , STAT6, phosphorylated-STAT4 (p-STAT4), and p-STAT6 were detected using Western blot. Serum levels of IFN-γ, IL-4, IL-6, and IL-10 were measured by ELISA. Effects of different concentrations baicalin on expressions of PBMCs, and levels of IFN-γ, IL-4, IL-10 of UC patients were also detected.</p><p><b>RESULTS</b>Compared with the negative control group, 40 µmol baicalin obviously decreased IL23R gene expression of UC patients (P <0. 01). Compared with the healthy control group and the IBS-D group, p-STAT4/STAT4 ratios increased, p-STAT6/STAT6 ratios decreased, levels of IFN-γ, IL-4, IL-10 all increased in the US group (all P <0. 05). Compared with the negative control, 5 and 10 µmol baicalin groups, 20 and 40 moL baicalin obviously decreased p-STAT4/STAT4 ratios (all P <0. 05); 20 and 40 µmoL baicalin obviously increased p-STAT6/STAT6 ratios (all P <0. 05); 20 and 40 µmoL baicalin obviously lowered levels of IFN-γ and IL-4, and elevated IL-10 levels (all P <0. 05).</p><p><b>CONCLUSION</b>40 µmoL baicalin could in vitro inhibit p-STAT4/STAT4 ratios, adjust p-STAT6/STAT6 ratios and related cytokines, thereby balancing the immunity and relieving inflammatory reactions of UC.</p>
Subject(s)
Humans , Activating Transcription Factors , Metabolism , Anti-Inflammatory Agents, Non-Steroidal , Therapeutic Uses , Blotting, Western , Colitis, Ulcerative , Drug Therapy , Metabolism , Cytokines , Metabolism , Flavonoids , Therapeutic Uses , Interleukin-10 , Metabolism , Interleukin-4 , Metabolism , Interleukin-6 , Metabolism , Irritable Bowel Syndrome , Drug Therapy , Metabolism , Leukocytes, Mononuclear , Medicine, Chinese Traditional , Phosphorylation , STAT6 Transcription Factor , Metabolism , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells.</p><p><b>METHODS</b>Firstly, we constructed the ZFP-ATF plasmid, then testified the quantity of VEGF protein in EY.HY926 endothelial cells after transfected with ZFP-ATP plasmid by Western blot, finally, we used the RT-PCR to testify whether the ZFP-ATF can stimulate expression of VEGF splice variants.</p><p><b>RESULTS</b>The ZFP-ATF DNA sequences were located the multiclone sites of PVAX1 vector between the site of BamH1and Xhol.Western blot result showed VEGF expression in EY.HY926 endothelial cells transfected with ZFP-ATF plasmid was significantly higher than that in cells transfected with VEGF165 (19.95±3.95 vs.12.15±1.55 μg÷μL, P<0.01).RT-PCR result showed VEGF-A mRNA expression level induced by ZFP-ATF was high than that induced by VEGF165.</p><p><b>CONCLUSION</b>ZFP-ATF can up-regulate the VEGF-A expression in comparison with VEGF165, which might have beneficial effects in angiogenesis process.</p>