ATP depletion-induced actin rearrangement reduces cell adhesion via p38 MAPK-HSP27 signaling in renal proximal tubule cells.

Ischemia causes desquamation of proximal tubular epithelial cells leading to acute renal failure. However, the molecular mechanisms underlying the detachment of proximal tubule cells remain unknown. In this study, we reported that ATP depletion resulted in actin polymerization, a shift of filamentous actin from web-like structure to fragmented parallel stress fibers, followed by a reduction of cellular adhesion ability. The pre-treatment with Jasplakinolide, an actin stabilizer, prevented ATP depletion-induced actin polymerization and reduction of cell adhesion, indicating that the cytoskeleton reorganization decreased the cellular adhesion ability. Furthermore, the ATP depletion markedly increased the levels of p38MAPK and HSP27 phosphorylation with enhanced translocation of phosphorylated HSP27 from cytoskeleton to cytoplasm. The inhibition of p38MAPK by SB203580 blocked the ATP depletion to induce HSP27 phosphorylation and actin polymerization. These findings suggest that ischemia remodels filamentous actin leading to desquamation of proximal tubular epithelial cells through p38 MAPK-HSP27 signaling.