Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells?
The antiproteinuric effect of cyclosporine A(CsA) has been believed to result from its immunosuppressive effect on the transcription factor NFAT in T cells. However, current evidences supporting this hypothesis are missing. A recent study showed that CsA has a direct antiproteinuric effect on podocy...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Nephrology |
| Online Access: | http://dx.doi.org/10.1155/2012/809456 |
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| author | Bin Zhang Wei Shi |
| author_facet | Bin Zhang Wei Shi |
| author_sort | Bin Zhang |
| collection | DOAJ |
| description | The antiproteinuric effect of cyclosporine A(CsA) has been believed to result from its immunosuppressive effect on the transcription factor NFAT in T cells. However, current evidences supporting this hypothesis are missing. A recent study showed that CsA has a direct antiproteinuric effect on podocytes, suggesting a novel non-immunosuppressive mechanism for CsA's antiproteinuric effect. Conditional NFATc1 activation in podoyctes per se is sufficient to induce proteinuria in mice, indicating that NFAT activation in podocytes is a critical pathogenic molecular event leading to podocyte injury and proteinuria. Meanwhile, evidence showed that TRPC6-mediated Ca2+ influx stimulates NFAT-dependent TRPC6 expression. Altogether, these advances in podocyte research indicate that calcineurin-NFAT signal or calcineurin-synaptopodin axis has a direct proteinuric effect on podocytes which raises the possibility of developing specific antiproteinuric drugs that lack the unwanted effects of calcineurin or NFAT inhibition. |
| format | Article |
| id | doaj-art-7dcf5f04c1cd4dc89fdcf6fa04e3daea |
| institution | Kabale University |
| issn | 2090-214X 2090-2158 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Nephrology |
| spelling | doaj-art-7dcf5f04c1cd4dc89fdcf6fa04e3daea2025-08-20T03:35:23ZengWileyInternational Journal of Nephrology2090-214X2090-21582012-01-01201210.1155/2012/809456809456Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells?Bin Zhang0Wei Shi1Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan No. 2 Road, Guangzhou 510080, ChinaDepartment of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan No. 2 Road, Guangzhou 510080, ChinaThe antiproteinuric effect of cyclosporine A(CsA) has been believed to result from its immunosuppressive effect on the transcription factor NFAT in T cells. However, current evidences supporting this hypothesis are missing. A recent study showed that CsA has a direct antiproteinuric effect on podocytes, suggesting a novel non-immunosuppressive mechanism for CsA's antiproteinuric effect. Conditional NFATc1 activation in podoyctes per se is sufficient to induce proteinuria in mice, indicating that NFAT activation in podocytes is a critical pathogenic molecular event leading to podocyte injury and proteinuria. Meanwhile, evidence showed that TRPC6-mediated Ca2+ influx stimulates NFAT-dependent TRPC6 expression. Altogether, these advances in podocyte research indicate that calcineurin-NFAT signal or calcineurin-synaptopodin axis has a direct proteinuric effect on podocytes which raises the possibility of developing specific antiproteinuric drugs that lack the unwanted effects of calcineurin or NFAT inhibition.http://dx.doi.org/10.1155/2012/809456 |
| spellingShingle | Bin Zhang Wei Shi Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? International Journal of Nephrology |
| title | Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? |
| title_full | Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? |
| title_fullStr | Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? |
| title_full_unstemmed | Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? |
| title_short | Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells? |
| title_sort | is the antiproteinuric effect of cyclosporine a independent of its immunosuppressive function in t cells |
| url | http://dx.doi.org/10.1155/2012/809456 |
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