Abstract: SA-PO677
CD44 Isoform Status Predicts Response to Treatment in Childhood Nephrotic Syndrome
Session Information
- Pediatric Glomerular Disease
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Herman-Edelstein, Michal, Rabin Medical Center, Ramat-Gan, Israel
- Fisher, Dor, schneider children''s medical center, Ramat-Gan, Israel
- Rozen-zvi, Benaya, Rabin Medical Center, Ramat-Gan, Israel
- Davidovits, Miriam, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel
Background
Standard CD44 (sCD44) and variant (vCD44) isoforms are hyaluronic receptors , known as stem cell markers that play a role in stem cell activation, migration, and shaping of extracellular matrix and fibrosis. De-novo expression of CD44 is a marker of activated glomerular parietal cells (PECs), which predicts the development of focal segmental glomerulosclerosis (FSGS). Upregulation of CD44 in nephrotic syndrome (NS) has been linked to poor prognosis in minimal-change disease (MCD) and has been shown to be an early marker of glomerular sclerosis prior to the development of visible lesions by light microscopy. Multiple CD44 isoforms are known to produce by alternative RNA splicing with different functions related to cell-cell ,cell-matrix interaction and also to renal fibrosis, however, there are no reports on which isoforms are expressed on activated PECs in NS and whether changing profile of CD44 isoforms expression is associated with renal disease progression. This study was addressed to investigate the role of different CD44 splicing variant isoforms expression in pediatric kidney biopsies of steroid responsive vs steroid resistant NS.
Methods
Here we investigate the expression patterns of CD44S (which does not contain any alternative exon) and CD44 splice variants using rtPCR in RNA isolated from formalin-fixed, paraffin-embedded (FFPE) of renal biopsies from children with nephrotic syndrome (n=40) versus normal kidneys (n=12), all were treated in our department.
Results
The expression of CD44S and CD44 splice variants CD44v2, CD44v6, and CD44v9/10, were significantly higher in NS kidneys compeerd with normal kidneys and were negatively correlated with disease progression and overall immunosuppressive response. In contrast, there was no significant difference in the expression of CD44v3, CD44v4/5, and CD44v7.
Conclusion
These data indicate that certain standart CD44 and CD44 splice variants may contribute to NS pathology and to disease progression and glomerulosclerosis.