ACTH action on podocytes: mystery solved?
ACTH action on podocytes: mystery solved?
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ACTH 对足细胞的作用：谜团解开了？
DOI：
10.1152/ajprenal.00139.2016
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Campbell,KirkN
中科院分区：
文献类型：
--
作者：
Cravedi,Paolo;Campbell,KirkN
PODOCYTES are the key target cell for injury in proteinuric kidney disorders such as focal segmental glomerulosclerosis (FSGS), minimal change disease, and membranous nephropathy. Sadly, advances in elucidating the molecular architectural details of the podocyte actin cytoskeleton, cell body, and intervening slit diaphragm have not yet translated into targeted therapeutic agents for clinical use. For over 60 yr, nephrologists have been treating glomerular diseases with repurposed, nonspecific immunosuppressive drugs, such as steroids and alkylating agents. Clinical responses have been variable with wide side effect profiles, further highlighting the need for the development of agents with a clear mechanistic rationale for their use.Quite often, the podocyte-specific rationale for using these agents is deciphered years after their widespread use becomes commonplace. For example, the B cell-depleting antibody Rituximab was initially used to treat patients with membranous nephropathy by reducing anti-phospholipase A2 receptor autoantibody titers (10a). More recently, Rituximab has been shown also to stabilize sphingomyelinase-like phosphodiesterase 3b protein expressed on podocyte cell membranes, possibly explaining its efficacy in treating recurrent FSGS posttransplant (7). Similarly, dexamethasone stabilizes the podocyte actin cytoskeleton in response to puromycin aminonucleoside-mediated injury (10), and cyclosporine prevents the degradation of the actin-bundling protein synaptopodin by calcineurin-mediated dephosphorylation (6). Direct protective effects on podocytes have also been reported for other immunomodulatory drugs, including levamisole and mycophenolate mofetil (11).
