In Vitro Evidence for a Direct Antifibrotic Role of the Immunosuppressive Drug Mycophenolate Mofetil

@article{Roos2007InVE,
  title={In Vitro Evidence for a Direct Antifibrotic Role of the Immunosuppressive Drug Mycophenolate Mofetil},
  author={Nina Roos and Nicolas Poulalhon and Dominique Farge and Isabelle Madelaine and Alain Mauviel and Franck Verrecchia},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2007},
  volume={321},
  pages={583 - 589}
}
The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent organ rejection after transplantation and has shown some efficacy to prevent the fibrotic complications that occur during autoimmune diseases such as systemic sclerosis or during graft-versus-host disease (GVHD). We tested the hypothesis that MMF may exert direct effects on fibroblast extracellular matrix remodeling. Incubation of human lung fibroblast cultures with MMF led to dose- and time-dependent reduction in the… 
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108 Citations
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108 Citations

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Citation Type

Der Einfluss von Mycophenolat-Mofetil (MMF) auf die renale Fibrogenese: Bedeutung für neue therapeutische Ansätze
TLDR
The results indicate that MPA treatment in addition to an IMPDH-dependent inhibition of fibroblast proliferation and wound closure may also cause an IM PDH-independent inhibition of collagen matrix contraction.
Effects of Mycophenolic Acid on Human Fibroblast Proliferation, Migration and Adhesion In Vitro and In Vivo
  • C. Morath, H. Reuter, +8 authors M. Zeier
  • Medicine, Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2008
TLDR
A downregulation of the cytoskeletal proteins vinculin, actin and tubulin in fibroblasts exposed to pharmacological doses of MPA is shown using microarray technology, real‐time polymerase chain reaction (PCR) and Western blot.
Immunosuppressive Drugs Alter α1-Antitrypsin Production in Hepatocytes: Implications for Epithelial Gap Repair.
Evidence of an antifibrotic effect of immunosuppressive drugs: applications in the treatment of systemic sclerosis
TLDR
A better understanding of the pathogenesis of tissue fibrosis and of the pivotal role of extracellular matrix components supports the use of various immunosuppressive drugs to treat systemic sclerosis.
The emerging role of mycophenolate mofetil in interstitial lung diseases
TLDR
Though results are limited, immunosuppressants such as MMF have shown promise as an effective and well-tolerated steroid-sparing agent, providing hope that the limited treatment armamentarium for ILDs can be expanded.
Mycophenolic acid in rheumatology: mechanisms of action and severe adverse events.
TLDR
Given the differences in sensitivity to MPA among the various cell types and the great inter-individual variability in MPA pharmacokinetics, adequate daily doses and therapeutic drug monitoring may be decisive to ensure those MPA concentrations needed to switch off inflammation and restore peripheral tolerance in autoimmune disease patients.
Anti-fibrotic effect of mycophenolate mofetil on Peyronie’s disease experimentally induced with TGF-β
TLDR
The injection of TGF-β promoted fibrotic alterations in the penile tunica albuginea in Wistar rats corresponding to PD in this model, MMF acts as a regenerating anti-fibrotic agent.
Mycophenolic Acid Displays IMPDH-Dependent and IMPDH-Independent Effects on Renal Fibroblast Proliferation and Function
TLDR
The results indicate that MPA treatment leads to inosine monophosphate dehydrogenase (IMPDH)-dependent inhibition of fibroblast proliferation and wound closure as well as an unexpected IMPDH-independent inhibition of collagen matrix contraction.
[Do specific antifibrotic properties of immunosuppressive drugs used in the treatment of systemic sclerosis exist?].
Mycophenolic acid inhibits the phosphorylation of nuclear factor‑κB and Akt in renal tubular epithelial cells.
TLDR
The results of the present study suggested that MPA may exert its anti‑fibrotic effects by inhibiting the upregulation of TGF‑β1 and the activation of NF‑κB following albumin overload, which may be partly dependent on the Akt pathway.
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TLDR
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