The response of mesangial cells to a phlogistic challenge includes cell proliferation and mesangial matrix expansion. Cell proliferation is a highly regulated process which includes enhancing factors such as
cyclins,
cyclin dependent kinases, and inhibitory
proteins, such as p27(kip1). The aim of the study was to evaluate the effects of
Mycophenolate mofetil (MMF), and
roscovitine (R), on the cell cycle regulatory system when administered in the florid phase of the experimental model of mesangial proliferative
nephritis induced by the anti
Thy-1 antigen monoclonal antibody. Three days after
nephritis induction, different groups were given MMF and R. Rats treated with MMF or R showed a slight decrease in mesangial proliferation and matrix expansion. Samples of cortical tissue were tested by 'real time' RT-PCR in order to study gene expression of
cyclins B, D1, D2, D3, E, and the
cyclin inhibitor p27(kip1). Localization of
mRNA was evaluated by in situ hybridization. Real time RT-PCR analysis showed a significant decrease in
cyclins B, D1, D2, and D3 in rats treated with either MMF or R as compared to controls. Both MMF and R treatment induced a significant increase in p27(kip1)
mRNA expression. In situ hybridization showed a mesangial-endothelial expression pattern in glomeruli. The number of labelled cells per glomerulus, the number of positive glomeruli in each examined slide as well as
cyclin D2 and D3 signal intensity was significantly lower in rats treated with MMF or R as compared to controls, whereas MMF or R treatment up-regulated p27(kip1)
mRNA expression. Immunohistochemical evaluation of p27(kip1) aimed to examine the influence of MMF or R on
protein expression confirmed up-regulation.