[HTML][HTML] Specific inhibition of Egr-1 prevents mesangial cell hypercellularity in experimental nephritis

M Carl, Y Akagi, S Weidner, Y Isaka, E Imai… - Kidney international, 2003 - Elsevier
M Carl, Y Akagi, S Weidner, Y Isaka, E Imai, HD Rupprecht
Kidney international, 2003Elsevier
Specific inhibition of Egr-1 prevents mesangial cell hypercellularity in experimental nephritis.
Background Mesangial cell proliferation is a frequent finding in glomerulonephritis. In
cultured mesangial cells, we demonstrated that inhibition of the zinc finger transcription
factor, early growth response gene-1 (Egr-1), by specific antisense oligonucleotides (AS
ODN) blocks mesangial cell proliferation. Therefore, we here investigated the effect of Egr-1
inhibition on the course of an experimental mesangioproliferative glomerulonephritis in vivo …
Specific inhibition of Egr-1 prevents mesangial cell hypercellularity in experimental nephritis.
Background
Mesangial cell proliferation is a frequent finding in glomerulonephritis. In cultured mesangial cells, we demonstrated that inhibition of the zinc finger transcription factor, early growth response gene-1 (Egr-1), by specific antisense oligonucleotides (AS ODN) blocks mesangial cell proliferation. Therefore, we here investigated the effect of Egr-1 inhibition on the course of an experimental mesangioproliferative glomerulonephritis in vivo.
Methods
On day 3 after induction of anti-Thy-1.1 nephritis, specific glomerular oligonucleotide transfer was achieved by injection of an oligonucleotide/hemagglutinating virus of Japan/liposome mixture into the left renal artery. The right kidney was left untreated.
Results
Induction of nephritis led to a sixfold induction of Egr-1 protein on day 6 of disease. This increase in Egr-1 expression was reduced by 48% in the left kidney by transfer of specific AS ODN. In parallel, the increases in glomerular cellularity, number of mitoses, and glomerular tuft area observed in day 6 nephritic animals were inhibited in the left kidney by 60%, 53%, and 50%, respectively. Changes in the right kidney were not significantly influenced. Likewise, control oligonucleotides showed no effect. Finally, the expression of platelet-derived growth factor-B (PDGF-B), a known target gene of Egr-1, was repressed by transfer of specific AS ODN against Egr-1.
Conclusion
We conclude that the transcription factor Egr-1 plays a critical role for mesangial cell proliferation in vivo. Interfering with the induction of Egr-1 or with its target genes could give rise to novel therapeutic principles in mesangioproliferative glomerulonephritis.
Elsevier