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- 저자 : 조상경(Sang Kyoung Jo) (검색결과 3 건)
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고농도 포도당에서 배양한 혈관사이질 세포에서 안지오텐신 ll와 안지오텐신 전환효소 억제제가 Procollagen α₁(lV) m RNA 발현에 미치는 효과
임천규(Chun Gyoo Ihm),이소영(So Young Lee),차대룡(Dae Ryong Cha),조원용(Won Yong Cho),한상엽(Sang Yup Han),김형규(Hyoung Kyu Kim),조상경(Sang Kyoung Jo),윤종우(Jong Woo Yoon),김용섭(Yong Seup Kim),이정호(Jung Ho Lee) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1
N/A Objective: Diverse glomerular disorders leadsing to progressive glomerulosclerosis share the common features of increased mRNA expression for extra- cellular matrix protein and growth factors. The precise role of angiotensin II in contributing to these disturbances is currently unknown. ACE inhibitors have been proved to be beneficial in protecting against glomerular injury in animal models and many of human glomerular diseases. Type IV collagen is a main component of extracellular matrix in the mesangium : its increased accumulation is a common pathologic finding in the glomerulosclerosis. There are some evidences that the beneficial effect of ACE inhibitor does not solely depend on the hemodynamic effect, but may be mediated by other effect. The purpose of this study is to evaluate the effects of high glucose, angiotensin II and angiotensin converting enzyme inhibitor on the expression of PCa₁(lV) in mesansial cells(MCs). Methods: Human mesangial cells were cultured with standard method. To investigate the effect of each drug and high glucose condition, MCs were cultured in the normal-glucose medium(100mg/dl) and high-glucose medium(450mg/dl), respectively. An- giotensin II and angiotensin converting enzyme inhibitor(captopril) were added to culture medium at final concentration of 10 M which is the physiologic dose in vivo. MCs were cultured in each condition for 3days, when the maximal effect of high glucose on MCs, and harvested for mesurement of the expression of PCa₁(IV) mRNA. To quantitate the PCa(1V) mRNA levels in each condition, semiquantitatine RT-PCR was done with co-amplification of house keeping gene. Results: PCa₁(IV) mRNA expression was significantly increased in high-glucose medium(30mM) compared to normal-glucose medium(5.5mM)(2.28±0.34 vs 0.96±0.08, p<0.05). Administration of angiotensin ll(10(-6)M) in culture media induced a further increment in the PC a >(IV) mRNA expression to 4.64±0.28(p<0.05). Angiotensin II in the normal-glucose medium increased the PCa₁(lV) mHNA expression as 2.69±0.23 control(p<0.05). Addition of angiotensin converting enzyme inhibitor(Capopril, 10(-6)M) in high- glucose culture medium significantly suppressed the PCar(IV) mRNA expression as 0.690.11(p<0.05). Conclusion: High glucose concentration in culture medium significantly increases the mRNA expression of procollagen alphal(IV) than normal glucose concentration. Angiotensin II increases the collagen mRNA expression directly and this effect was significantly prevented by ACE inhibitor. This result suggests that hyperglycemia in diabetic millieu can directly increase collagen production, and ACE inhibitor may inhibit progressive glomerulosclerosis by decreasing collagen production as well as reducing intraglomerular pressure.
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배양된 메산지움세포에서 고농도 포도당, 안지오텐신 II 및 안지오텐신 전환효소 억제제가 TGFβ 유전자 발현에 미치는 효과
이소영,김형규,윤종우,차대룡,조원용,강민모,곽재영,임천규,한상엽,조상경 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.4
Objective:Diabetic nephropathy is an important cause of end stage renal disease in Korea and associated with major morbidity and mortality. The precise pathogenic mechanism of this disease is still controversial, but it has been considered that multiple factors are contribute to the development and progression of diabetic nephropathy. One of these factors, renin-angiotensin system has been proven to be a major mediator of this disease via activation of angiotensin II, which has multiple functions such as induction of production of extracellular matrix protein and various intraglomerular cells, tubulointerstital component and increment of intraglomerular pressure. Transforming growth factor(TGFβ) is a multifunctional cytokine with major profibrotic character, which stimulates the production of extracellular matrx(ECM) protein, inhibit the degradation of ECM and induce the interaction of mesangial cells with ECM via integrin receptors. This study was done to evaluate the role of angiotensin II and angiotensionverting enzyme inhibitor in expression of TGFβ mRNA which is a main mediator in the pathogenesis of diabetic nephropathy. Methods:Human mesangial cells(MCs) were cultured by standard culture techniqne. For this study, cells in the 5th to 7th passage were used. To make a different glucose concentration in culture medium, normal(100mg/dl) or high glucose(450mg/dl) concentrations of D-glucose were added, and cultured in 17% heat inactivated fetal bovine serum. Angiotensin II and ACE inhibitor(captopril) were administered to the culture medium at final concentration of 10-6M. After 72 hours, MCs were harvested to measure the expression of TGFβ mRNA. To measure the mRNA expression of TGFβ in each condition, semi quantitative PCR was done and all results were corrected by β-actin gene. Results:mRNA expression of TGFβ was significantly increased in the high glucose medium(30 mM) compared to normal glucose medium(5.5mM) (3.82±0.465 vs 2.27±0.13, p$lt;0.05). Administration of angiotensin II(10-6M) in high gluum induced a further increase in the TGFβ expression to 4.29±0.476(p$lt;0.05). Angiotensin II(10-6M) in normal glucose medium also showed a significant increase in TGFβ expression as 3.40±1.88(p$lt;0.05). Administration of ACE inhibitor(Captopril, 10-6M) in high glucose medium prevented the increse of TGFβ expression(1.20±0.18 vs 3.82±0.465, p$lt;0.05). Conclusion:From these findings, it suggest that angiotensin II is an important mediator in the pathogenesis of diabetic nephropathy. ACE inhibitor may have a role in the progress of this disease via direct suppression of TGF? system as well as beneficial intraglomerular hemodynamic effect.
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