|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1994 : ¥900,000 (Direct Cost : ¥900,000)
In the present study, we examined the effect of extracellular matrix (ECM) produced by either glomerular endothelial cells (GEnC) or mesangial cells (MC) on the morphology, mitotic activity and gene expressions of extracellular matrix components in MC.It was further clarified whether the effect of GEnC-derived ECM on mesangial cell morphology and function can be modified by the treatment of GEnC with an angiotensin converting enzyme inhibitor (ACEI), captopril.
It was clearly demonstrated that GEnC-derived ECM significantly suppressed mesangial cell elongation and proliferation compared to MC-derived ECM,and mesangial cell growth on the ECM produced by captopril-treated GEnC was further attenuated, compared to the ECM produced by untreated GEnC.Northern blot analysis revealed that GEnC exposed to captopril for 48hr had two three fold increase in mRNA levels for type IV procollagen [C-IV ; alpha1 (IV)], heparan sulfate proteoglycan (HSPG) compared to untreated GEnC (280% and 218%, respectively). Moreover, MC cultured on the the ECM produced by captopril-treated GEnC had a marked decrease in C-IV mRNA levels by 50%, compared to that on the ECM produced by untreated GEnC,whereas fibronectin mRNA levels in MC were not different between the ECM produced by captopril-treated and untreated GEnC.This observation suggests that the expression of C-IV can be down-regulated in MC grown on the ECM with an increased amount of C-IV.These results also indicate that ACEI can modulate MC growth through stimulating GEnC to produce membrane-type ECM and GEnC-derived ECM may have a role in regulation MC function. We are in the process of examining the effect of mesangial cell interaction with ECM on tyrosine-specific protein phosphorylation in MC,in order to elucidate whether enhanced tyrosine phosphorylation of certain protein (s) may be associated with the changes in morphology, mitotic activity and ECM production of MC.