Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

Abstract:

:Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.

journal_name

Lupus

journal_title

Lupus

authors

Cheng CC,Lee YF,Lan JL,Wu MJ,Hsieh TY,Lin NN,Wang JM,Chiu YT

doi

10.1177/0961203313480398

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

554-61

issue

6

eissn

0961-2033

issn

1477-0962

pii

0961203313480398

journal_volume

22

pub_type

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