Abstract
Recent data suggest that neurotrophic factors that derive from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line‐derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by yet undefined processes. Here we investigated whether GDNF directly affects intestinal epithelial barrier functions. Permeability (PE) was estimated by measurements of 4 kD FITC‐dextran flux across differentiated and across immature Caco2 monolayers. Recombinant human GDNF (100 ng/ml) was applied for 24h to test possible effects on epithelial barrier functions. GDNF application resulted in significant epithelial barrier stabilisation only in Caco monolayers with immature barrier functions. This effect was paralleled by a more linearized and augmented staining pattern of tight junction proteins claudin1 and occludin at the cell borders. Barrier maturation by GDNF correlated with augmented cAMP‐levels in immature Caco2 cells. Moreover, wound healing assays showed a significantly faster closure of the wounded areas following application of GDNF.These data show that GDNF directly affects intestinal epithelial cells and promotes epithelial wound healing and barrier maturation. This effect may be mediated by augmented cAMP levels following GDNF application.Grant Funding Source: Supported by DFG
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