van Roeyen, Claudia R. C. and Eitner, Frank and Boor, Peter and Moeller, Marcus J. and Raffetseder, Ute and Hanssen, Lydia and Buecher, Eva and Villa, Luigi and Banas, Miriam C. and Hudkins, Kelly L. and Alpers, Charles E. and Ostendorf, Tammo and Floege, Juergen (2011) Induction of progressive glomerulonephritis by podocyte-specific overexpression of platelet-derived growth factor-D. KIDNEY INTERNATIONAL, 80 (12). pp. 1292-1305. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
Platelet-derived growth factor-D (PDGF-D), normally expressed in podocytes, mediates mesangial cell proliferation in vivo. To study this further, we created transgenic mice with podocyte-specific overexpression of PDGF-D. Hemizygous mice were grossly indistinguishable from wild-type littermates through 11 months of age; however, hemizygous mice older than 4 weeks commonly exhibited increased cell proliferation within the glomerular tuft. Many hemizygous mice also developed widespread segmental glomerulosclerosis and focal extracapillary proliferation with fibrin/fibrinogen deposition, extensive tubulointerstitial damage, proteinuria, and renal insufficiency. Electron microscopy found focal foot process effacement. Renal mRNA expression of podocin and nephrin, as well as the number of glomerular WT-1-positive cells, were significantly reduced in hemizygous compared to wild-type mice, indicating loss and/or dedifferentation of podocytes. PDGF-A, -B, and both PDGF receptor chain mRNAs, fibronectin, type IV collagen, RANTES, MCP-1, and CCR-2 mRNAs were all increased in the renal cortex of PDGF-D transgenic mice. Only 8.5% of newborn mice were homozygous overexpressors exhibiting a mortality rate of 37% at 4 weeks. Thus, podocyte-specific overexpression of PDGF-D caused mesangioproliferative disease, glomerulosclerosis, and crescentic glomerulonephritis. Hence, podocyte-specific growth factor overexpression can induce paracrine mesangial cell proliferation upstream of the filtration flow.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESANGIAL CELL-PROLIFERATION; PROTEASE-ACTIVATED LIGAND; PDGF-C; MURINE MODEL; EXPRESSION; RECEPTOR; KIDNEY; MICE; GLOMERULOSCLEROSIS; CRESCENTS; glomerulonephritis; podocyte; transgenic mouse |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 May 2020 09:37 |
| Last Modified: | 26 May 2020 09:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19750 |
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