title: Antifibrotic actions of mycophenolic acid.
abstract: Mycophenolic acid (MPA) is a highly selective, non-competitive and reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides. Mycophenolate mofetil (MMF, the ester prodrug of MPA) strongly inhibits both T- and B-lymphocyte proliferation and has now been widely used in the prevention of acute and chronic allograft rejection. Recent evidence, however, suggests that MMF is also capable of inhibiting the proliferation of non-immune cells. In various cell lines, e.g. smooth muscle cells, renal tubular cells, mesangial cells, and fibroblasts, MPA reduced or even abrogated proliferation in response to proliferative stimuli. In animal studies, MMF ameliorated renal lesions in immune-mediated disease, e.g. in the Anti-Thy 1.1 model and experimental lupus nephritis, but was also effective in non-immune-mediated renal damage, e.g. in the rat remnant kidney model or in a model of chronic cyclosporine nephrotoxicity in the rat. In humans, MMF reduced proteinuria in steroid-resistant nephrotic syndrome and had beneficial effects in the prevention and treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity through the reduction of immune- and non-immune-mediated renal damage. MMF is well tolerated and has proven to be a relatively safe drug. Taken together, there is a growing body of evidence pointing to therapeutic applications of MMF other than immunosuppression, in particular the prevention of fibrosis.
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany. christian_morath@med.uni-heidelberg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Morath
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
authors.forename: Jörg
authors.initials: J
authors.lastname: Beimler
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Walter
authors.initials: W
authors.lastname: Muranyi
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid