Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion

Roeder SS, Barnes TJ, Lee JS, Kato I, Eng DG, Kaverina NV, Sunseri MW, Daniel C, Amann KU, Pippin JW, Shankland SJ (2017)


Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 91

Pages Range: 896-913

Journal Issue: 4

DOI: 10.1016/j.kint.2016.10.015

Abstract

The glycoprotein CD44 is barely detected in normal mouse and human glomeruli, but is increased in glomerular parietal epithelial cells following podocyte injury in focal segmental glomerulosclerosis (FSGS). To determine the biological role and regulation of CD44 in these cells, we employed an in vivo and in vitro approach. Experimental FSGS was induced in CD44 knockout and wild-type mice with a cytotoxic podocyte antibody. Albuminuria, focal and global glomerulosclerosis (periodic acid-Schiff stain), and collagen IV staining were lower in CD44 knockout compared with wild-type mice with FSGS. Parietal epithelial cells had lower migration from Bowman's capsule to the glomerular tuft in CD44 knockout mice with disease compared with wild type mice. In cultured murine parietal epithelial cells, overexpressing CD44 with a retroviral vector encoding CD44 was accompanied by significantly increased collagen IV expression and parietal epithelial cell migration. Because our results showed de novo co-staining for activated ERK1/2 (pERK) in parietal epithelial cells in experimental FSGS, and also in biopsies from patients with FSGS, two in vitro strategies were employed to prove that pERK regulated CD44 levels. First, mouse parietal epithelial cells were infected with a retroviral vector for the upstream kinase MEK-DD to increase pERK, which was accompanied by increased CD44 levels. Second, in CD44-overexpressing parietal epithelial cells, decreasing pERK with U0126 was accompanied by reduced CD44. Finally, parietal epithelial cell migration was higher in cells with increased and reduced in cells with decreased pERK. Thus, pERK is a regulator of CD44 expression, and increased CD44 expression leads to a pro-sclerotic and migratory parietal epithelial cell phenotype.

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APA:

Roeder, S.S., Barnes, T.J., Lee, J.S., Kato, I., Eng, D.G., Kaverina, N.V.,... Shankland, S.J. (2017). Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion. Kidney International, 91(4), 896-913. https://dx.doi.org/10.1016/j.kint.2016.10.015

MLA:

Roeder, Sebastian S., et al. "Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion." Kidney International 91.4 (2017): 896-913.

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