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The Effect Of Adiponectin On Proliferation And Expression Of Tgf-β1mRNA And BMP-7mRNA In Human Mesangial Cells Cultured Under High Glucose

Posted on:2013-07-14Degree:MasterType:Thesis
Country:ChinaCandidate:J C WuFull Text:PDF
GTID:2234330371477664Subject:Internal Medicine : Endocrine
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Background:Diabetic nephropathy is one of the most common chronic complications and the main causes of death of diabetes mellitus. The main pathological alteration is the accumulation of extracellular matrix aggregation on renal tubular and renal glomerulus. Accordingly, it can result in glomerular sclerosis and renal interstitial fibrosis. The prevention and cure to progression of kidney fibrosis has already been the focus of diabetic nephropathy research, now,Transformation growth factor-β1(TGF-β1) was found the most powerful promote fibrosis factor, while bone morphogenetic proteins-7(BMPS-7) is an anti fibrosis factor, both in the occurrence of DN development plays an important role. Adiponectin is to find having various Biology activity in recent years. Numerous studies have demonstrated that adiponectin has multiple functions, such as, anti-inflammatory, antiatheroscierotic and anti-fibrosis, but the role of ADPN is still ambiguous in kidney. Therefore, The experiment makes use of extracorporeal culture human mesangial cells (HMC) to study the effect of TGF-β1mRNA and BMP-7mRNA, to discuss the effect of ADPN in DN.Objective:To investigate the effect of high glucose on the expression transforming growth factor-β1(TGF-β1)mRNA and bone morphogenetic protein-7(BMP-7)in human mesangial cells(HMC),and to further study the intervention of adiponectin(ADPN).To illuminate the potential protection of ADPN on the kidney.Methods:①The HMC were allocated into3groups:normal glucose group(5.5mol/L glucose,NG), high glucose group(30.0mmol/L glucose, HG), HG+ADPN group(30.0mmol/L glucose+2.5μg/ml adiponectin),After HMC was cultured with upper three different kinds of environments for24h,48h,96h,the proliferation activity of HMC was observed by MTT.②The HMC were allocated into3groups:normal glucose group(5.5mmol/L glucose,NG), high glucose group(30.0mmol/L glucose,HG), HG+ADPN group(30.0mmol/L glucose+2.5μg/ml adiponectin).After HMC was cultured with upper three differends of environments for24h,48h,72h, the expressions of TGF-β1mRNA and BMP-7mRNA were assayed with reverse transcription polymerase chain reaction (RT-PCR).Results:①Compared with NG group,proliferation activity of HMC was promoted in high glucose group in the early(24h-48h),but it was inhibited later(96h).And compared with HG group,proliferation activity of HMC increased time-dependently in low concentration adiponectin group(2.5μg/ml);②HG could active signifieantly increase in synthesis of TGF-β1mRNA and the over expression of these factors were significantly inhibited by Preincubation with adiponectin,the ADPN-suppression effect was the most significant at48h. At the same time, ADPN could increase the expression of BMP-7mRNA while HG inhibit the expression of BMP-7mRNA.Conclusion:The high glucose could inhibit the proliferation activity of HMC,promote the expression of TGF-β1mRNA while inhibit the expression of BMP-7mRNA.The adiponectin(2.5μg/ml)could promote the proliferation activity of HMC and the expression of BMP-7mRNA,but could inhibit the expression of TGF-β1mRNA.The results suggest that adiponectin maybe protect the kidney of patients with DM by decreasing the expression of TGF-β1mRNA and increasing the expression of BMP-7mRNA,and provide a new method to prevention and cure complications of diabetes.
Keywords/Search Tags:adiponectin, mesangial cells, Transforming growth factor-β1(TGF-β1), bonemorphogenic protein-7(BMP-7)
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