Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis.

Abstract:

BACKGROUND/AIMS:De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice). METHODS:As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application. RESULTS:After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of Lotus tetragonolobus lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74. CONCLUSION:Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression.

journal_name

Nephron

journal_title

Nephron

authors

Yamazaki T,Sasaki S,Okamoto T,Sato Y,Hayashi A,Ariga T

doi

10.1159/000448221

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

238-252

issue

4

eissn

1660-8151

issn

2235-3186

pii

000448221

journal_volume

134

pub_type

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