NDLI: Mannose-6-Phosphate/Insulin-Like Growth Factor-II Receptors may Represent a Target for the Selective Delivery of Mycophenolic Acid to Fibrogenic Cells

Content Provider	Springer Nature Link
Author	Greupink, Rick Bakker, Hester I. Goor, Harry Borst, Martin H. Beljaars, Leonie Poelstra, Klaas
Copyright Year	2006
Abstract	The insulin-like growth factor axis plays an important role in fibrogenesis. However, little is known about mannose-6-phosphate/Insulin-like growth factor-II receptor (M6P/IGF-IIR) expression during fibrosis. When expressed preferentially on fibrogenic cells, this receptor may be used to selectively deliver drugs to these cells. We investigated M6P/IGF-IIR expression in livers of bile duct-ligated (BDL) rats and in renal vascular walls of renin transgenic TGR(mRen2)27 rats. Both models are characterized by fibrogenic processes. Furthermore, we studied whether drug delivery via M6P/IGF-II-receptor-mediated uptake is possible in fibroblasts.M6P/IGF-IIR mRNA expression was investigated 3, 7 and 10 days after BDL. At all time-points hepatic M6P/IGF-IIR expression was significantly increased compared to healthy controls. Moreover, immunohistochemical staining revealed that α-sma-positive cells were M6P/IGF-IIR-positive. In kidneys of TGR(mRen2)27 rats, the number of M6P/IGF-IIR-positive arteries per microscopic field was increased 5.5 fold over healthy controls. To examine whether M6P/IGF-IIRs could be used as a port of entry for drugs, we coupled mycophenolic acid (MPA) to mannose-6-phosphate-modified human serum albumin (M6PHSA). M6PHSA-MPA inhibited 3T3-fibroblast proliferation dose-dependently, which was reversed by co-incubation with excess M6PHSA, but not by HSA.M6P/IGF-IIRs are expressed by fibrogenic cells and may be used for receptor-mediated intracellular delivery of the antifibrogenic drug MPA.
Starting Page	1827
Ending Page	1834
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	8
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2006-07-19
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	drug targeting liver fibrosis mycophenolic acid TGR(mRen2)27 rats vascular lesions Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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