کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6856 522 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of pH on molecular mechanisms of chitosan–integrin interactions and resulting tight-junction disruptions
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Effects of pH on molecular mechanisms of chitosan–integrin interactions and resulting tight-junction disruptions
چکیده انگلیسی

Chitosan (CS) is a potential paracellular permeation enhancer for trans-epithelial drug delivery; however, its ability to enhance epithelial permeability in a pH-dependent manner remains unclear. This study was designed to explore the underlying molecular mechanisms with regard to the effect of CS on tight junction (TJ) disruption at different pH environments in Caco-2 cell monolayers. The experimental results revealed that the direct interaction between CS and integrin αVβ3 on cell surfaces has a crucial role in CS-induced TJ opening, an indication of receptor activation. The mechanism of action appeared to be the electrostatic interaction between the positively-charged CS and the negatively-charged integrin αVβ3. This electrostatic interaction led to the conformation change of integrin αVβ3 and its clustering along the cell border, F-actin reorganization, and CLDN4 down-regulation, eventually resulting in the disruption of TJs and an increase in paracellular permeability. The above observations were all in a pH-dependent manner. As pH increased, CS became less positively charged, thereby losing its capability to interact with integrin αVβ3 and failing to induce the TJ opening. These consequences might help to better understand the molecular mechanism of TJ opening mediated by CS, thereby facilitating the use of CS for trans-epithelial drug delivery.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 3, January 2013, Pages 784–793
نویسندگان
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