title: 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.
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung City 40705, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Cheng
authors.forename: Y-F
authors.initials: YF
authors.lastname: Lee
authors.forename: J-L
authors.initials: JL
authors.lastname: Lan
authors.forename: M-J
authors.initials: MJ
authors.lastname: Wu
authors.forename: T-Y
authors.initials: TY
authors.lastname: Hsieh
authors.forename: N-N
authors.initials: NN
authors.lastname: Lin
authors.forename: J-M
authors.initials: JM
authors.lastname: Wang
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chiu
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D007166:Immunosuppressive Agents; D055293:Receptors, Urokinase Plasminogen Activator; D009173:Mycophenolic Acid
keywords: lupus nephritis; mycophenolate mofetil; uPAR