Involvement of extracellular signal-regulated kinase and p38 in human diabetic nephropathy

Background: The involvement of mitogen-activated protein kinase (MAPK) in human diabetic nephropathy has not been fully investigated. Methods: The presence of cells positive for the phosphorylated MAPK family (phosphorylated extracellular signal-regulated kinase [p-ERK], phosphorylated p38MAPK [p-p38MAPK]) was investigated immunohistochemically in kidneys of 30 patients with diabetic nephropathy. In addition, 10 patients with minimal change nephrotic syndrome, 10 patients with thin basement membrane disease, and 5 patients with benign nephrosclerosis were studied as disease controls. The presence of activated nuclear factor-κB (p65)–positive cells also was evaluated in kidney specimens. Results: In patients with diabetic nephropathy, p-ERK, p-p38MAPK, and p65 were observed in mesangial cells, endothelial cells, podocytes, tubular epithelial cells, and mononuclear infiltrates in interstitium. Numbers of p-ERK–, p-p38MAPK–, and p65-positive cells in both glomeruli and interstitium in patients with diabetic nephropathy were higher than those in controls. In particular, the number of glomerular p-ERK–positive cells in patients with diabetic nephropathy increased in accordance with the progression of glomerular lesions and correlated well with the number of glomerular p65-positive cells ( r = 0.654; P r = 0.757; P r = 0.647; P r = 0.605; P