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Comparison of mucosal absorption-enhancing activity between a claudin-3/-4 binder and a broadly specific claudin binder.

Abstract：

:Intercellular spaces between adjacent mucosal epithelial cells are sealed by tight junctions (TJs) that prevent the free movement of solutes across the epithelium. Claudins (CLs), a family of 27 integral membrane proteins, are essential components for TJ seals. We previously used a CL-3/-4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), to show that CL modulation is a promising method to enhance mucosal absorption. Recently, by using a C-CPE mutant library, we developed a CL binder (m19) with broad specificity to CL-1, -2, -4, and -5. Here, we compared the mucosal absorption-enhancing activity of C-CPE and m19. Both CL binders enhanced jejunal absorption of dextran with a molecular mass of 4000 and 150,000 Da and nasal absorption of dextran with a mass of 4000 Da but not 150,000 Da in rats. Although both binders showed similar nasal absorption-enhancing activity of dextran (4000 Da), m19 exhibited a more potent jejunal absorption-enhancing effect than that of C-CPE. These findings suggest that mucosal absorption-enhancing activity may be modified by modulating CL specificity.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Matsuhisa K,Kondoh M,Suzuki H,Yagi K

doi

10.1016/j.bbrc.2012.05.060

subject

Has Abstract

pub_date

2012-06-29 00:00:00

pages

229-33

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)00937-0

journal_volume

423

pub_type

杂志文章

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