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Study On The Expression Of Metalloproteinase-9 And Transform Growth Factor-β1 And Mutual Regulation In Peripheral Blood Monocytes In Patients With Hypertention And Renal Arteriosclerosis

Posted on:2003-11-02Degree:MasterType:Thesis
Country:ChinaCandidate:J P SunFull Text:PDF
GTID:2144360062496430Subject:Pathogenic microbiology
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Objective To investigate the role of expression of Metalloproteinase-9 and Transform Growth Factor-Pi of mRNA and mutual regulation in peripheral Blood Monocytes in the development and progression of patients with hypertention( HP) and renal arterio-sclerosis(HN) and renal failure(HNF).Methods mRNA Expression of Metalloproteinase-9 and Transform Growth Factor-(3j were detected by reverse transcription-PCR(PT-PCR) in peripheral Blood Monocytes in patients with hypertention(HP) and renal arteriosclerosis ( HN) and renal failure (HNF) of different stages. cDNA was synthesized with reverse transcription from RNA extracted from peripheral monocytes and was exemplified with PCR. After electrophre-sis,it was photoed digitally and was scanned with VIDAS21 analytical system. The relative content of MMP-9and TGF-ftwas expressed with Odof MMP-9 bandand was analyzed with SPSS stastical software.Results There was a significantly higher level of expression of MMP-9 mRNA in HN and HNF than that in healthy control (HC)(P<0. 01), and no difference between HP and NC. A higner level of TGF-ft mRNA expression was noted in HP, HN and HNF than that in healthy control (HC)(P<0. 01). MMP-9 mRNA followed the rise of TGF-ftmRNA.Discussion Faoming cells are the major cellular component of atherosclerotic plaque,origination gfrom peripheral monocytes and macrophages. Human monocytes secrete MMP-9and the activated monocytes participate in the degradation and transportation of extracellular matrix. MMPs might be the initiating factor for the formation of atherosclerosis. Its role in the enchancemant of the degradation and transport of ECM participates in the formation of plaque and vascular remodeling. High level of MMP-9 mRNA expression in peripheral monocytes in patients with primary HN suggests themonocytic expression of MMP-9 mRNA induced by long-term hypertension, which might destroy the intactness of arterial wall and glomerulolar basement membrane through induction of degradation of collagen IV, leading to increased ermeability of glo-merular membrane manifested by haematuria, proteinuria. These play a important role in the formation and progression of HN. TCP-Pi, a kind of secretary protein, was expressed in different stages of diseases and was proved to be important in tissue repair and could faciliate the accumulation of ECM. It had been proven that (masangeal cells), epithelium of glomerulus and renal tubular interstitial cells could secret TGF-J3 and TGF-P was considered to facilitate the synthesis of ECM protein by and a important cy-tokine for the glomerular masangeal accumulation. Its role persisted in the progression of hypertension in term of atherosclerosis, glomerular atrophy and hypertrophy and renal interstitial fibrosis. In this study, the expression of TGF-frmRNA was increased progressively in HP,HN,HNF of different stages of hypertension in comparison to controls with statistical significance(P<0. 01). This suggested the important role of TGF-Pi in the formation and progression of primary HN. It was also found an dose-dependent increase in the expression of glomerular MMp-2 and MMP-9 mRNA induced by TGF-P in vitro. In this investigation, a significantly higher level of expression of TGF-f3i in HP group, whereas no change in MMP-9expression was noted. It is suggestive that expression of TCP-Pi took place earlier than that of MMP-9 and MMP-9 was regulated by TGF-ft.Our results strongly suggested that the expression level of MMP-9 and TGF-pj mRNA are higner in peripheral Blood Monocytes with hypertention(HP) and renal arteriole arteriosclerosis(HN) and renal failure(HNF).Conclusion Our result showed that MMP-9 and TCP-Pi may contribute to vascular remodeling during the development and progression of hypertention(HP) and renal arteriole arteriosclerosis(HN) and renal failure(HNF). Meanwhile, MMP-9may memediat-ed remodeling of glomerular basement membrane (GBM) and urinary protein excretion by degrading collagen type IV and destroying the framework of GBM,which play an im-portment role in the developme...
Keywords/Search Tags:Metalloproteinase-9(MMP-9), Transform Growth Factor-1 (TGF-β1), Gene expression, Remodeling of glomerular basement membrane (GBM)
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