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.
Zhang
Mei
M
Renal Division, Department of Medicine, First Hospital, and Institute of Nephrology, Peking University, Beijing, People's Republic of China.
Tang
Jiawei
J
Li
Xiaomei
X
D000199:Actins / Q000096:biosynthesis; D000873:Anthracenes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007633:Keratins / Q000096:biosynthesis; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000199:Actins; D000873:Anthracenes; D005353:Fibronectins; D005419:Flavonoids; D007093:Imidazoles; D007375:Interleukin-1; D011725:Pyridines; C432165:pyrazolanthrone; D007633:Keratins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one