Article ; Online: The podocyte as a direct target of glucocorticoids in nephrotic syndrome.
2021 Volume 37, Issue 10, Page(s) 1808–1815
Abstract: Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one or multiple ... ...
| Abstract | Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one or multiple relapses and prolonged use may be associated with severe adverse effects. Recently the beneficial effects of glucocorticoids have been attributed to a direct effect on podocytes in addition to the well-known immunosuppressive effects. The molecular effects of glucocorticoid action have been studied using animal and cell models of NS. This review provides a comprehensive overview of different molecular mediators regulated by glucocorticoids, including an overview of the model systems that were used to study them. Glucocorticoids are described to stimulate podocyte recovery by restoring pro-survival signalling of slit diaphragm-related proteins and limiting inflammatory responses. Of special interest is the effect of glucocorticoids on stabilizing the cytoskeleton of podocytes, since these effects are also described for other therapeutic agents used in NS, such as cyclosporin. Current models provide much insight but do not fully recapitulate the human condition since the pathophysiology underlying NS is poorly understood. New and promising models include the glomerulus-on-a-chip and kidney organoids, which have the potential to be further developed into functional NS models in the future. |
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| MeSH term(s) | Animals ; Cyclosporins/metabolism ; Cyclosporins/pharmacology ; Cyclosporins/therapeutic use ; Glucocorticoids/pharmacology ; Glucocorticoids/therapeutic use ; Humans ; Kidney Glomerulus/metabolism ; Nephrotic Syndrome/drug therapy ; Nephrotic Syndrome/metabolism ; Podocytes/metabolism |
| Chemical Substances | Cyclosporins ; Glucocorticoids |
| Language | English |
| Publishing date | 2021-01-29 |
| Publishing country | England |
| Document type | Journal Article ; Review ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 90594-x |
| ISSN | 1460-2385 ; 0931-0509 |
| ISSN (online) | 1460-2385 |
| ISSN | 0931-0509 |
| DOI | 10.1093/ndt/gfab016 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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