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The Study of Effects of Emodin on Expression of Gremlin1 in Renal Tubular Epithelial Cells Induced by TGF-β1

Author: DuanShuZhong
Tutor: WangJianQin
School: Lanzhou University
Course: Kidney disease medicine
Keywords: HK-2 Gremlin1 Emodin TGF-β1 BMP α-SMA
CLC: R285.5
Type: Master's thesis
Year: 2008
Downloads: 122
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Abstract


Objective:To study the relationship between Gremlin,and TIF,and research the effect of Emodin on expression of Gremlin,in renal tubular epithelial cells induced by TGF-β1.Method:（1）Basing on culturing human kidney tubular epithelial cells（HK-2）,take the group of cell induced by TGF-β1to EMT as positive control.Dvide into five groups:A:Serum free as control,B:TGF-β1 （2ng/ml）,C:TGF-β1（2ng/ml）+Emodin（10 ug/ml）,D:TGF-β1（2ng/ml） +Emodin（20 ug/ml）,E:TGF-β1（2ng/ml）+Emodin（40 ug/ml）（2）After treating for 12 h、24 h、48 h,detect the mRNA expression of Gremlin by Real-time PCR and the Gremlin protein expression by Western blotting.（3）Select 40 case biopsy specimens of patient troubled with different type of primary glomerular nephritis.The tubulointerstitial injuries is graded into four degree groups according to the extent of cortical interstitial fibrosis.Then the of Gremlin1 are investigated with immunohistochemistry assays.Results:（1）2ng/ml TGF-β1 promote the process of HK-2 transdifferen -tiation to myofibroblast and the exepression of Gremlin1,after culturing for 24h and 48h.（2）The expression of Gremlin mRNA and protein reduce gradually（P＜0.05）,according to up-regulation of the Emodin concentration （10 ug/ml、20 ug/ml、40 ug/ml）.（3）Gremlin expression was not detected in normal adult human kidney.Gremlin expression was most pronounced in areas of tubulointerstitial fibrosis. Conclusion:（1）TGF-β1 can promote the expression of Gremlin, （2）Gremlin1 expression is up-regulation in renal tissue with tubulointerstitial fibrosis.According to the aggravated extent of fibrosis,the Gremlin1 expression is up-regulation,and there is a positive correlation with renal fuction dysfunction.Greml in,may pay a important role in renal fibrosis and lower renal function,so Gremlin1 could be regards as index to judge the degree of fibrosis,and potential target to cure renal disease.（3）Emodin can inhibit the promotion effect of TGF-β1 on Gremlin,expression.

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