Abstract
In recent decades, the global prevalence of diabetes has provided a warning of chronic complications. Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes that affects approximately 35% of diabetic individuals. DN is the main cause of end-stage kidney disease, in which the kidneys can no longer function on their own. Podocytes in the glomerulus play a critical role in regulating glomerular permeability, and podocyte injury is the main cause of DN. Therefore, an increasing number of studies have focused on podocyte injury in DN, and interventions targeting podocyte injury have emerged as potential therapeutic strategies against DN. Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family that plays critical roles in intracellular signal transduction. In human patients with DN, phosphorylated ERK (pERK), the active form of ERK, is increased in the glomerulus. However, information on the expression of pERK, specifically in podocytes in DN, is limited. Meanwhile, high glucose induces ERK activation in immortalized podocyte cell lines, suggesting the involvement of podocytic ERK in DN. We performed an immunohistochemical study to investigate whether podocytic pERK levels increase in patientswith DN. In comparison to healthy controls, patients with DN showed significantly increased pERK expression levels in cells that were positive for the podocyte-specific marker Wilms’ tumor-1 (DN: 51.3 ± 13.1% vs. Control: 7.3 ± 1.6%, p = 0.0158, t-test, n = 4 for each group). This suggests that ERK activation in podocytes is involved in the pathogenesis of DN.