Specific inhibition of Egr-1 prevents mesangial cell hypercellularity in experimental nephritis
| Autor: | Sven Weidner, Yoshitaka Isaka, Harald D. Rupprecht, Enyu Imai, Marina Carl, Yoshitaka Akagi |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Glomerulonephritis Membranoproliferative antisense medicine.medical_treatment Mitosis Biology Sendai virus Immediate-Early Proteins Rats Sprague-Dawley Isoantibodies In vivo Internal medicine medicine Animals mesangioproliferative glomerulonephritis transcription factor Early Growth Response Protein 1 Kidney Mesangial cell Growth factor Gene Transfer Techniques Glomerulonephritis Proto-Oncogene Proteins c-sis Oligonucleotides Antisense medicine.disease Molecular biology Glomerular Mesangium Rats DNA-Binding Proteins body regions Endocrinology medicine.anatomical_structure Nephrology liposome Liposomes Immediate early gene Nephritis Cell Division hormones hormone substitutes and hormone antagonists immediate early gene Transcription Factors Kidney disease |
| Zdroj: | Kidney International. 63(4):1302-1312 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.2003.00865.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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