대한신장학회

논문분류	춘계학술대회 초록집
제목	Effect of α-Spinasterol on Induction of Thrombospondin-1 by High Glucose in Cultured Mesangial Cells
저자	Jung Sub Song, Yu Min Lee, Ju Hung Song, Seon Ho Ahn
출판정보	2013; 2013(1):
키워드	당뇨병성 신병증, 트롬보스폰딘-1, 사이간질 세포/Diabetic nephropathy, Mesangial cell, Thrombospondin-1
초록	Background: Transforming growth factor-β (TGF-β) is the central cytokine responsible for the development of diabetic nephropathy. It is recently reported that thrombospondin-1 (TSP-1) is the major activator of latent TGF-β in diabetic nephropathy in vivo. We suggested previously that α-spinasterol may be a promising therapeutic substance able to ameliorate the development and progression of diabetic nephropathy by inhibiting TGF-β production. However, it has not been investigated how α-spinasterol inhibit TGF-β production. So this study is to examine the effect of α- spinasterol on TSP-1 production and downstream target of TGF-β through TSP-1 induced by high glucose in cultured mesangial cells. Methods: Mouse mesangial cells were incubated for 24 hour with normal (5.6 mM) or high (30 mM) glucosecontaining medium in the presence or absence of α-spinasterol (1 ng/mL). Mesangial proliferation was determined by counting cell number. Real time qRT-PCR was performed to observe the TSP-1, TβRI, and TβRII mRNA expression. TSP-1, Smad2/3, TIMP2, and MMP2 protein expression in medium or cell lysate were determined by western blot. Gelatin zymography was performed for the measurement of MMP2 activity in medium. Results: α-spinasterol inhibited the high glucose-stimulated proliferation of mouse mesangial cells, but did not affected to the growth of mouse mesangial cells cultured under normal glucose. TSP-1 mRNA expression and protein expression was increased in cultured mouse mesangial cells under the high glucose concentration. α-spinasterol attenuated TSP-1 mRNA expression and protein expression in cultured mouse mesangial cells under the high glucose. Also, α- spinasterol inhibited TSP-1 protein expression in medium of cultured mouse mesangial cells under the high glucose. Smad2/3 activity was increased in high glucose-stimulated mesangial cell, but decreased by α-spinasterol. TIMP2/ MMP2 ratio in cultured medium or cell lysate was decreased by α-spinasterol. MMP2 acitivity on gelatin zymography was similar to MMP2 protein expression in same medium. Conclusion: We demonstrated that α-spinasterol attenuated TSP-1 protein expression in cultured mouse mesangial cells under the high glucose, and resulted in regulating cell proliferation, and TIMP2/MMP2 ratio through TGF-β/ Smad2/3 signaling.This result suggests that α-spinasterol may be considered as a promising future treatment option for diabetic nephropathy.
원문(PDF)	PDF 원문보기

간행물 검색

대한신장학회 회원관리 규정