Extracellular signal-regulated kinase is activated in podocytes from patients with diabetic nephropathy.

Autor: Yamashiro A; Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Saitama, Japan. ayamashiro@ndmc.ac.jp., Satoh Y; Department of Biochemistry, National Defense Medical College, Tokorozawa, Saitama, Japan. wndlt3@gmail.com., Endo S; Aging Neuroscience Research Team, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo, Japan., Oshima N; Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Jazyk: angličtina
Zdroj: Human cell [Hum Cell] 2024 Sep; Vol. 37 (5), pp. 1553-1558. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1007/s13577-024-01108-4
Abstrakt: In the past few decades, the global prevalence of diabetes has provided us with a warning about future chronic complications. Diabetic nephropathy (DN) is the main cause of end-stage kidney disease. Podocytes in the glomerulus play a critical role in regulating glomerular permeability, and podocyte injury is one of the main causes of 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 glomeruli. 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 using Wilms' tumor-1 (WT-1) as a podocyte-specific marker to investigate whether podocytic pERK levels are increased in patients with DN. In the glomeruli of the DN group, we observed remarkable co-staining for WT-1 and pERK. In contrast, the glomeruli of the control group contained only a few pERK-positive podocytes. Statistical analyses revealed that, relative to healthy controls, patients with DN showed significantly increased pERK expression levels in cells that were positive for WT-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.
(© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)
Databáze: MEDLINE
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