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- Title
Mesangial cell expression of proto-oncogene Ets-1 during progression of mesangioproliferative glomerulonephritis.
- Authors
Raffetseder, Ute; Wernert, Nico; Ostendorf, Tammo; van roeyen, Claudia; Rauen, Thomas; Behrens, Peter; Floege, Jurgen; Mertens, Peter R.
- Abstract
Mesangial cell expression of proto-oncogene Ets-1 during progression of mesangioproliferative glomerulonephritis. Background. Ets-1 is a transactivator of matrix-associated genes and key factor in neoangiogenesis. The expression of Ets-1 mRNA and protein was analyzed in healthy rat kidney and in a model for mesangioproliferative disease without and with inhibition of platelet-derived growth factor-B (PDGF-B) activity. Methods. Immunohistochemistry was performed using a specific noncrossreacting anti-Ets-1 antibody and included a counterstain with α-smooth muscle actin (α-SMA). Nuclear proteins from isolated glomeruli were analyzed by Western blotting. Changes in Ets-1 mRNA levels were detected by in situ hybridization and Northern blotting. PDGF-B antagonism was performed in nephritic rats by specific aptamers. Results. The distribution of Ets-1–positive cells in healthy rats was heterogenous with exclusively nuclear staining of glomerular, tubular, and vascular cells. Profound changes were detected in the anti-Thy 1.1 glomerulonephritis. Nuclear Ets-1 staining was intense in mesangial cells, whereas podocyte and endothelial cell staining was unchanged. The strongest signal was seen on days 2 to 7. By Western blotting of glomerular proteins a single 52 kD band was detected in healthy rats, which was increased 4.5-fold after disease induction. At the same time a 54 kD band appeared that most likely represents phosphorylated Ets-1. Ets-1 transcripts were detected in mesangial cells that include exon IV but lack exon VII. A concordant 6.4-fold up-regulation of mRNA was detected in glomeruli. Specific PDGF-B antagonism by aptamer treatment from days 3 to 7 after disease induction led to reduced Ets-1 expression on day 7, correlating with decreased mesangial cell numbers. Conclusion. A temporal increase of mesangial cell Ets-1 expression correlates with mesangial cell activation in mesangioproliferative glomerulonephritis. PDGF-B may partiallycontribute to the increased expression.
- Subjects
ONCOGENES; GLOMERULONEPHRITIS; IMMUNE complex diseases; MESSENGER RNA; GROWTH factors; IMMUNOHISTOCHEMISTRY
- Publication
Kidney International, 2004, Vol 66, Issue 2, p622
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1111/j.1523-1755.2004.00782.x