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Construction of Recombinant shRNA-espressing Vectors Targeting to Two Different Hepatic Fibrosis-related Cytokines
Author: LiuJiaQun
Tutor: ZhangJianJun
School: Luzhou Medical College
Course: Internal Medicine
Keywords: RNA interference Liver fibrosis Plasmid vector Connective tissue growth factor Tissue inhibitor of metalloproteinase factor-1
CLC: R575.2
Type: Master's thesis
Year: 2009
Downloads: 33
Quote: 0
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Abstract
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Objective: connective tissue growth factor (CTGF) is a recently discovered an important cytokine promoting liver fibrosis , transforming growth factor- β ( transforming growth factorβ TGF- β ) signaling pathway downstream effects of media . CTGF can directly mediated activation of primary hepatic stellate cells (hepatic stellate cell, HSC) proliferation and migration , but also promote the activation of HSC synthesis and secretion of extracellular matrix ( extracellular matrix , ECM) . Metal tissue inhibitor of metalloproteinase 1 (TIMP-1) of TGF-β signaling pathways downstream effects of media , liver fibrosis , which is mainly expressed by activated HSC . TIMP-1 not only inhibits the activity of matrix metalloproteinases (matrix metalloproteinase, MMPs) to prevent degradation of collagen , and play a key role in the progression of liver fibrosis also promote collagen secretion by inhibiting apoptosis of HSC . Therefore, to reduce the expression of CTGF and TIMP-1 , can reduce the degree of liver fibrosis . This study aimed to construct the the rat CTGF or TIMP-1 gene targeting short hairpin RNA (short hairpin RNA, shRNA) expression vector , to provide a powerful tool to further explore the gene therapy of liver fibrosis . Methods: RNA interference target CTGF and TIMP-1 gene is the most effective pre- screened , that CTGF gene 1560 ~ 1580nt and TIMP -1 gene 412 ~~ 432nt RNA interference ( RNA interference , RNAi), sequence design principles each design containing short hairpin RNAi target sequences , annealing to form a double-stranded DNA , were cloned into the recombinant plasmid vector containing the purpose of the target gene fragment psiRNA-GFP construct by double digestion of the plasmid vector psiRNA - h7SKGFPzeo the -CTGF and psiRNA - of GFP- of TIMP- 1 , and the recombinant plasmids were double digested agarose gel electrophoresis and sequencing . Results: digestion confirmed to rat CTGF or TIMP-1 gene to target the expression of the shRNA target gene fragments were cloned into plasmid vector psiRNA-h7SKGFPzeo sequencing results show that the insertion sequence of the recombinant plasmid vector design target gene fragment is completely consistent . Conclusion : The successful construction of targeting rat CTGF and TIMP-1 of the most effective RNA interference target shRNA expression plasmid recombinant lay the experimental basis for further exploration of new ways of hepatic fibrosis gene therapy .
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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Cirrhosis
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