內科HSIEH, BOR-SHENBOR-SHENHSIEHTSAI, TUN-JENTUN-JENTSAICHEN, YUNG-MINGYUNG-MINGCHEN林水龍2009-09-292018-07-112009-09-292018-07-112005http://ntur.lib.ntu.edu.tw//handle/246246/93082This study was designed to investigate the effect of 1- benzyl-3-(5′- hydroxymethyl-2′-furyl) indazole (YC-1), a guanylate cyclase activator, upon the proliferation of rat mesangial cells and its underlying mechanism . YC-1 inhibited cell proliferation and DNA synthesis in a dose- and time- dependent manner. Flow cytometry cell-cycle studies revealed that YC-1 prevented the entry of cells from G1 into S phase . The expression of cyclin D1 and the kinase activity of cyclin D1/cyclin-dependent kinase ( CDK)4 were lower within YC-1-treated cells, revealed by Western blotting, Northern blotting and kinase assays. YC-1 did not increase the intracellular cGMP concentration in mesangial cells. Inhibitors of soluble guanylate cyclase, protein kinase G, or protein kinase A also did not reverse the inhibitory effect elicited by YC-1, while co-treatment with p 38 mitogen -activated protein kinase (MAPK) inhibitor could partially reverse the suppressive effect. YC-1 inhibited proliferation of mesangial cells and induced cell-cycle arrest by the reduction of cyclin D1 synthesis and cyclin D1/CDK4 kinase activity. This effect acts partially through p38 MAPK signal transduction activation and is independent of cGMP - signaling pathways.en-USp38 mitogen-activated protein kinaseProliferationCyclin D1Mesangial cellsYC-1journal article