Changes in Laminin beta 1 Chain Expression in Renal Cortex by the Intervention with Cilazapril and Losartan on Adriamycin-Induced Nephropathy

Kim, Tai Jin; Chung, Ho Sam; Paik, Doo Jin; Youn, Jee Hee; Kim, Won Kyu

Abstract

Laminin, an extracellular matrix glycoprotein, is distributed in the basement membrane of renal glomerulus. Laminin has been demonstrated to regulate the development and differentiation of glomeruli and play an important role in the filtering function of glomeruli. To address whether laminin beta 1 chain is associated with the pathogenic states of renal injury and recovery, nephropathy were induced by intravenous adriamycin injection and subsequently cured by treatment with antihypertensive drugs, cilazapril (angiotensin-converting enzyme inhibitor, ACEi) and lozartan (angiotensin receptor blockade, ARB), which have been known to be effective on renal protection. The results we obtained were as follows: 1. At 6 and 12 weeks after adriamycin injection, epithelial cells of proximal convoluted tubules exhibited intensive deposition of laminin beta 1 chain reactive gold particles. Cytoplasm of podocytes and mesangial cells in glomeruli showed an increase in the gold particle deposition as compared with that of controls. The mRNA level of laminin beta 1 chain was enhanced in the epithelial cells of proximal convoluted tubules. 2. Following cilazapril administration to adriamycin -induced nephropathy rats, laminin beta 1 chain reactive gold particle deposition was reduced in the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. The level of laminin beta 1 chain transcripts was remarkably decreased in the epithelial cells of proximal convoluted tubules. 3. Following losartan administration to adriamycin -induced nephropathy rats, podocytes and mesangial cells were deposited with reduced number of laminin beta 1 chain reactive gold particles. The laminin beta 1 chain reactive gold particles and level of laminin beta 1 chain mRNA transcripts were remarkably reduced in the epithelial cells of proximal convoluted tubules. 4. Treatment with mixture of cilazapril and losartan to adriamycin -induced nephropathy rat resulted in a decrease in laminin beta 1 chain reactive gold particle deposition within the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. Laminin beta 1 chain mRNA expression in the epithelial cells of proximal convoluted tubules nearly disappeared. These results consequently suggest that laminin beta 1 chain may be synthesized within the epithelial cells of proximal convoluted tubules, podocytes and mesangial cells and laminin beta 1 chain may play an important role on tissue recovery of the renal tissues injured by adriamycin.