RESUMEN
Renal tubulointerstitial injury induced by albumin overload is a critical stage during the progression of renal interstitial fibrosis and progression of chronic renal diseases. Inosine5'monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is known to attenuate the progression of renal interstitial fibrosis; however, the underlying molecular mechanisms of the antiï¬brotic effects of derivatives of MMF have not yet been studied. The present study assessed the effects of the MPA on renal tubular epithelial cells. Transforming growth factor beta 1 (TGFß1) has been indicated to have a central role in the underlying molecular mechanisms of renal fibrosis; furthermore, nuclear transcription factorκB (NFκB) is a transcription factor associated with the production of inflammatory cytokines, cell proliferation and apoptosis. In addition, the Akt signaling pathway has important roles in cell proliferation, differentiation, metabolism and apoptosis. The present study subjected the NRK52E rat kidney epithelialderived cell line to albumin overload, which resulted in an increase in TGFß1 production as well as phosphorylation of Akt and the binding activity of NFκB to the promoter region of the TGFß1 gene, which was, however, reduced following preincubation of the cells with MPA. In addition, the effects of albumin were partially blocked by Ly294002, a specific inhibitor of Akt. In conclusion, the results of the present study suggested that MPA may exert its antifibrotic effects by inhibiting the upregulation of TGFß1 and the activation of NFκB following albumin overload, which may be partly dependent on the Akt pathway.