Single application of low-dose mycophenolate mofetil-OX7-immunoliposomes ameliorates experimental mesangial proliferative glomerulonephritis

Suana, A J; Tuffin, G; Frey, B M; Knudsen, L; Mühlfeld, C; Rödder, S; Marti, H-P (2011). Single application of low-dose mycophenolate mofetil-OX7-immunoliposomes ameliorates experimental mesangial proliferative glomerulonephritis. Journal of pharmacology and experimental therapeutics, 337(2), pp. 411-22. Bethesda, Md.: American Society for Pharmacology and Experimental Therapeutics 10.1124/jpet.110.176222

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IgA nephropathy, one of the most frequent forms of glomerulonephritis, characterized by mesangial hypercellularity and glomerular extracellular matrix (ECM) expansion, often leads to end-stage renal disease over a prolonged period. We investigated whether antiproliferative treatment in a single low dose specifically targeted to the glomerular mesangium by immunoliposomes (ILs) results in an amelioration of mesangial proliferative glomerulonephritis in rats (anti-Thy1.1 nephritis). Mycophenolate mofetil (MMF) containing ILs was generated that targets the Thy1.1 antigen (OX-7) in rat mesangial cells. Treatment benefit of a single intravenous dose of these ILs given 2 days after disease induction was investigated by stereology, immunohistochemistry, and functional analyses (creatinine, albuminuria) until day +9 and was compared among untreated and free MMF-treated rats using six male Wistar rats per group. MMF-loaded OX7-IL prevented creatinine increase and albuminuria. Stereological analyses of MMF OX7-IL-treated animals yielded 30% reduction of mesangial cells on day +9 and a 40% reduction of glomerular ECM volume on day +5, compared with all of the other nephritic animals. Furthermore, at days +5 and +9 we observed decreased ECM content and decreased glomerular volume (day +5) in the MMF-OX7-IL-treated group compared with the nephritic group treated with free MMF. In conclusion, MMF-OX7-IL-based directed drug delivery represents a novel approach for treating mesangial cell-mediated forms of glomerulonephritis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Marti, Hans-Peter

ISSN:

0022-3565

Publisher:

American Society for Pharmacology and Experimental Therapeutics

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:25

Last Modified:

06 Dec 2013 13:30

Publisher DOI:

10.1124/jpet.110.176222

PubMed ID:

21349934

Web of Science ID:

000289671600009

URI:

https://boris.unibe.ch/id/eprint/8976 (FactScience: 214636)

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