Korean Journal of Nephrology 2000;19(1):12-21.

원저 : 고농도 포도당에서 배양한 혈관사이질 세포에서 안지오텐신 ll와 안지오텐신 전환효소 억제제가 Procollagen α₁(lV) m RNA 발현에 미치는 효과 (Effect of High Glucose, Angiotensin ll and Aniotenisn Converting Enzyme Inhibitor on the Expression of PCa₁(IV) mRNA in Cultured Human Mesangial Cells)

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)

Abstract

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.