| Autor: |
Adriana, Migliorini, Maria L, Angelotti, Shrikant R, Mulay, Onkar O, Kulkarni, Jana, Demleitner, Alexander, Dietrich, Costanza, Sagrinati, Lara, Ballerini, Anna, Peired, Stuart J, Shankland, Helen, Liapis, Paola, Romagnani, Hans-Joachim, Anders |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
The American journal of pathology. 183(2) |
| ISSN: |
1525-2191 |
| Popis: |
Interferon (IFN)-α and IFN-β are the central regulators of antiviral immunity but little is known about their roles in viral glomerulonephritis (eg, HIV nephropathy). We hypothesized that IFN-α and IFN-β would trigger local inflammation and podocyte loss. We found that both IFNs consistently activated human and mouse podocytes and parietal epithelial cells to express numerous IFN-stimulated genes. However, only IFN-β significantly induced podocyte death and increased the permeability of podocyte monolayers. In contrast, only IFN-α caused cell-cycle arrest and inhibited the migration of parietal epithelial cells. Both IFNs suppressed renal progenitor differentiation into mature podocytes. In Adriamycin nephropathy, injections with either IFN-α or IFN-β aggravated proteinuria, macrophage influx, and glomerulosclerosis. A detailed analysis showed that only IFN-β induced podocyte mitosis. This did not, however, lead to proliferation, but was associated with podocyte loss via podocyte detachment and/or mitotic podocyte death (mitotic catastrophe). We did not detect TUNEL-positive podocytes. Thus, IFN-α and IFN-β have both common and differential effects on podocytes and parietal epithelial cells, which together promote glomerulosclerosis by enhancing podocyte loss while suppressing podocyte regeneration from local progenitors. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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