Possible involvement of mitogen-activated protein kinase in the angiotensin II-induced fibronectin synthesis in renal interstitial fibroblasts.
Angiotensin II (AT II) is thought to be associated with the development of renal interstitial fibrosis. However, the molecular mechanisms of the interstitial fibrosis have not been extensively studied. We have examined the role of mitogen-activated protein kinases (MAPKs) on fibronectin (FN) accumulation in cultured normal rat kidney interstitial fibroblasts (NRK 49F cell line). AT II caused dose-dependent increases in FN accumulation and FN mRNA in these cells. AT II also activated the extracellular signal-regulated kinase (ERK) and p38 MAPK in the presence of AT II. These increases in FN accumulation and activation of MAPKs were inhibited with AT I receptor antagonist (ARB; CV-11974) in renal interstitial fibroblasts. The inhibitors against ERK (PD98059) and p38 MAPK (SB203580) significantly inhibited AT II-induced increases in FN mRNA. These findings suggest that the MAPKs play an important role in AT II-mediated renal interstitial fibrosis and that ARB may be useful for preventing renal interstitial fibrosis.
Sekine
Shizue
S
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Nitta
Kosaku
K
Uchida
Keiko
K
Yumura
Wako
W
Nihei
Hiroshi
H
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D000804:Angiotensin II; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases