Modulation of renal epithelial barrier function by mitogen-activated protein kinases (MAPKs): mechanism of XXXX -induced increase in transepithelial resistance.

@entity9472 @entity5732 @entity235 @entity23417 @entity1441 @entity205 @entity37492 @entity4286
BACKGROUND: @entity205 ( @entity9472 ) has been shown to increase transepithelial resistance in Madin-Darby @entity235 kidney (MDCK) cells, and the mechanism may involve altered phosphorylation of junctional proteins. In this study, we examine the effect of the @entity23417 and @entity37492 (MAPK) pathways on the basal transepithelial resistance (TER) and on the @entity9472 -induced increase in TER across MDCK monolayers. Here we present evidence that @entity9472 may be mediating some of its effects through activation of the @entity23417 MAPK pathway. METHODS: MDCK cells were treated with @entity9472 (4.2 micromol/L) and paracellular permeability was assessed by measuring TER. The role of the @entity23417 and the p38 MAPK pathways in modulating TER was investigated using the inhibitors @entity4286 and @entity5732 for @entity23417 and @entity1441 for p38. @entity23417 and p38 phosphorylation/activation was also examined by Western blot analysis. RESULTS: @entity9472 (4.2 micromol/L) increased the TER of MDCK monolayers. The @entity23417 inhibitor @entity4286 decreased basal TER and also ameliorated the @entity9472 -induced increase in TER. Similar results were found with the U0126 inhibitor of @entity23417 . The p38 inhibitor @entity1441 had no effect on the basal TER of the monolayers, however, @entity1441 significantly augmented the @entity9472 -induced increase in TER. @entity9472 was shown to significantly activate @entity23417 and this activation by @entity9472 was prevented by @entity4286 . Inhibition of the p38 pathway by @entity1441 also resulted in activation of @entity23417 and this activation of @entity23417 was further enhanced by @entity9472 . No effect of @entity9472 or the inhibitors @entity4286 or @entity1441 on p38 phosphorylation was detected. CONCLUSION: The results presented here suggest that activation of the @entity23417 MAPK cascade is important in the regulation of the paracellular permeability in MDCK cells. Activation of this pathway appears to be pivotal to the @entity9472 -induced increase in TER.
