Cell-type-specific activation of mitogen-activated protein kinases in PAN-induced progressive renal disease in rats.
We examined the time-course activation and the cell-type specific role of MAP kinases in puromycin aminonucleoside (PAN)-induced renal disease. The maximal activation of c-Jun-NH2-terminal kinase (JNK), extracellular signal regulated kinase (ERK), and p38 MAP kinase was detected on Days 52, 38, and 38 after PAN-treatment, respectively. p-JNK was localized in mesangial and proximal tubular cells at the early renal injury. It was expressed, therefore, in the inflammatory cells of tubulointerstitial lesions. While, p-ERK was markedly increased in the glomerular regions and macrophages p-p38 was observed in glomerular endothelial cells, tubular cells, and some inflammatory cells. The results show that the activation of MAP kinases in the early renal injury by PAN-treatment involves cellular changes such as cell proliferation or apoptosis in renal native cells. The activation of MAP kinases in infiltrated inflammatory cells and fibrotic cells plays an important role in destructive events such as glomerulosclerosis and tubulointerstitial fibrosis.
Park
Sang-Joon
SJ
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Jeong
Kyu-Shik
KS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007249:Inflammation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000201:enzymology*; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011692:Puromycin Aminonucleoside / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D011692:Puromycin Aminonucleoside; 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