Does chondroitin sulphate play an active role in barrier formation by normal human urothelial cell cultures?
BAUS ePoster online library. Phillips R.
Jun 26, 2018; 211324
Rebecca Phillips
Rebecca Phillips
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Introduction: Chondroitin sulphate (CS) has been described as contributing to the barrier function of the urothelium by forming a thick glycosaminoglycan (GAG) layer on the superficial surface. Various papers have suggested that a defect in this layer contributes to chronic inflammatory uropathies and this forms the basis of medical device therapies.

Materials and Methods: Immunohistochemistry of human urothelium with well-characterised antibodies to CS epitopes was used to assess the presence of CS on urothelium in situ. The role of exogenous CS on barrier formation was examined during differentiation of normal human urothelial cell cultures by monitoring transepithelial electrical resistance (TEER).

Results: Immunohistochemical studies supported the presence of CS within the stroma, but not as a superficial urothelial GAG layer.
Urothelial cell cultures exposed to chondroitin 4 or 6 sulphate during differentiation formed a tighter maximum barrier compared to non-treated controls (p=0.0087 and p=0.0403 respectively, one-way ANOVA, n=9 in each arm, three individual cell lines). A barrier formed earlier with chondroitin-6-sulphate compared to control where, by day 3, there was a statistically significant difference in TEER readings (p=0.0044, one-way ANOVA, n=6 replicates in each arm, two individual cell lines).

Conclusion: This study has demonstrated that CS enhances barrier formation by human urothelial cells in culture. Intense labelling of CS within the stroma, with no urothelial presence suggests the mode of action is unlikely to be a simple supplementation of a GAG layer. Further studies addressing mode of action are being pursued.
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