ABSTRACT
UNLABELLED: Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. METHODS: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-ß1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. RESULTS: We found that higher expression of Egr1 and TGF-ß1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-ß1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-ß1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-ß1 promoter. CONCLUSION: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-ß1.
Subject(s)
Early Growth Response Protein 1/metabolism , Glucose/pharmacology , Kidney Glomerulus/pathology , Mesangial Cells/metabolism , Animals , Cell Proliferation/drug effects , Cells, Cultured , Chromatin Immunoprecipitation , Collagen Type IV/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Extracellular Matrix/metabolism , Fibronectins/metabolism , Fibrosis , Gene Expression Regulation/drug effects , Mesangial Cells/drug effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , RNA, Small Interfering/metabolism , Rats, Inbred OLETF , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacologyABSTRACT
OBJECTIVE: To study the severity of periodontitis and risk factors in Chengdu. METHODS: 202 periodontitis patients (65 male, 137 female), aged from 25 to 60, were requested to fill a questionnaire. Probing depth (PD), clinical attachment level (CAL), gingival recession and bleeding on probing (BOP) on 6 sites of each tooth were measured and recorded. RESULTS: The mean PD, AL, gingival recession and BOP% of 202 subjects was (3.2 +/- 0.31) mm, (3.5 +/- 0.37) mm, (0.3 +/- 0.02) mm and 21.16%. 59% of subjects missed at least one tooth. 129 subjects suffered with initial to moderate periodontitis. 73 subject suffered with advanced periodontitis. 40, 86, 55 and 21 subjects had received college education, high school education, middle school education and primary school education. 18% of subjects had smoking history, 67% subjects had tea/coffee history, 66% of subjects had psychosocial problem, and only 8% of subjects had received regular periodontal treatment. There is no relationship between the severity of periodontitis and education. CONCLUSION: It is very important to develop an education program on oral healthy for people in Chengdu.
Subject(s)
Periodontal Attachment Loss , Periodontal Index , Adult , Female , Gingival Recession , Humans , Male , Middle Aged , Periodontitis , Risk FactorsABSTRACT
PURPOSE: The purpose of this study was to investigate the relationship between TNFalpha-308 gene polymorphisms and susceptibility to chronic periodontitis in Chinese patients. METHODS: DNA samples with buccal swabs were collected from 63 severe CP patients, 103 initial to moderate CP patients, and 80 healthy controls in Chinese Han nationality. The TNFA-308 gene polymorphisms were analyzed with PCR-RFLP. The data were analyzed by X(2) test using SPSS10.0. RESULTS: There were no significant genotype distribution differences of TNFA-308 between either two of the three subject groups. CONCLUSION: Further study was needed since we did not find the relationship between TNFA-308 gene polymorphism and periodontitis in this present study.
Subject(s)
Chronic Periodontitis/genetics , Genetic Predisposition to Disease , Tumor Necrosis Factor-alpha/genetics , Asian People/genetics , Case-Control Studies , Genotype , Humans , Polymorphism, Restriction Fragment LengthABSTRACT
OBJECTIVE: To investigate the association between Fc gamma receptor IIA gene polymorphism and susceptibility to chronic periodontitis in Chinese Han nationality. METHODS: DNA samples were collected with buccal swabs from 63 patients with severe chronic periodontitis(CP), 103 patients with mild to moderate CP and 80 healthy individuals as control. Polymorphism in Fc gamma receptor IIA gene cluster was analyzed with PCR-SSP. The genotype distribution and allele frequency among different groups were compared. RESULTS: It was found that the frequency of Fc gamma RIIA-R/R131 genotype was significantly higher in patients with severe CP (19.05%) compared to that of the healthy controls (P < 0.0125). CONCLUSION: The Fc gamma RIIA-R/R131 genotype may be one of the contributors for the increased susceptibility to severe CP in Chinese Han nationality.
