Interleukin-1beta-induced transdifferentiation of renal proximal tubular cells is mediated by activation of JNK and p38 MAPK.

Interleukin (IL)-1beta induces renal tubular epithelial cells to transdifferentiate to myofibroblasts, which express alpha-smooth muscle actin (alpha-SMA). To understand the signal transduction mechanisms involved in transdifferentiation, we examined the roles of mitogen-activated protein kinases (MAPKs) in IL-1beta-stimulated alpha-SMA expression and cell migration in the HK-2 human renal proximal tubular cell line. IL-1beta induced the transdifferentiation of renal proximal tubular cells, which was characterized by upregulated expression of alpha-SMA and increased cell migration. In addition, IL-1beta increased the activity of the three members of the MAPK family, ERK, JNK and p38 MAPK, in these cells. Both SP600125, a specific inhibitor of JNK, and SB203580, a specific inhibitor of p38 MAPK, suppressed the IL-1beta-induced expression of alpha-SMA and cell migration, but these effects were not observed with PD98059, a specific inhibitor of ERK. These results suggest that IL-1beta-induced HK-2 cell transdifferentiation is mediated, at least in part, through the activation of the JNK and p38 MAPK signaling pathways.