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BACKGROUND: Tissue injuries and pathological changes are often associated with changes in cell adhesion and reorganization of cytoskeletal structures. This is of particular relevance for renal epithelial cells, which form a highly regulated barrier along the nephron. Here, we investigated the effect of the calcium chelator EGTA on morphological alterations and changes in pro-fibrotic gene expression in proximal renal tubular epithelial cells. METHODS: Epithelial cells were exposed to EGTA alone or in combination with TGF -1, followed by the analysis of N-cadherin and paxillin localization and cytoskeletal rearrangement. The expression of connective tissue growth factor (CTGF), a pro-fibrotic protein regulated by alterations of cell morphology, was investigated. RESULTS: Even low concentrations of EGTA, which did not lead to the loss of cell-cell interactions or cell detachment, were sufficient to reduce N-cadherin binding, to rearrange focal adhesion, to induce CTGF expression, and to strongly enhance TGF -1-mediated signaling. These data indicate a substantial crosstalk between the changes in cell cytoskeletal structures at the cell-cell adhesions and the signaling of soluble mediators. CONCLUSIONS: By linking cell-cell and cell-matrix interactions with the regulation of pro-fibrotic signaling, our studies provide deeper insights into the physiological mechanisms underlying the natural regeneration and repair processes in the kidney.

Structural reorganization of the cytoskeleton contributes to the induction of pro-fibrotic connective tissue growth factor in tubular epithelial cells