| First Author | Migliorini A | Year | 2013 |
| Journal | Am J Pathol | Volume | 183 |
| Issue | 2 | Pages | 431-40 |
| PubMed ID | 23747509 | Mgi Jnum | J:199084 |
| Mgi Id | MGI:5500830 | Doi | 10.1016/j.ajpath.2013.04.017 |
| Citation | Migliorini A, et al. (2013) The Antiviral Cytokines IFN-alpha and IFN-beta Modulate Parietal Epithelial Cells and Promote Podocyte Loss: Implications for IFN Toxicity, Viral Glomerulonephritis, and Glomerular Regeneration. Am J Pathol 183(2):431-40 |
| abstractText | Interferon (IFN)-alpha and IFN-beta are the central regulators of antiviral immunity but little is known about their roles in viral glomerulonephritis (eg, HIV nephropathy). We hypothesized that IFN-alpha and IFN-beta 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-beta significantly induced podocyte death and increased the permeability of podocyte monolayers. In contrast, only IFN-alpha 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-alpha or IFN-beta aggravated proteinuria, macrophage influx, and glomerulosclerosis. A detailed analysis showed that only IFN-beta 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-alpha and IFN-beta 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. |
