Possible new druggable targets for the treatment of nephrosis. Perhaps we should find them in caveolea?
Nephrosis refers to a condition resulting from proteinuric kidney disease, leading to irreversible renal parenchymal damage and end-stage renal disease when left untreated. Furthermore, nephrosis appears to be a communicable disease carrying risks and complications to other organs such as the heart. Key pathophysiolgical processes involved in initiating and progressing renal damage in nephrosis and its complications may include altered glomerular hemodynamics after initial renal damage and loss of nephrons, nephrotoxicity of increased renal protein traffic enforcing intrinsic 'common pathway' mechanisms of renal scarring, and generalized endothelial dysfunction proceeding CV disease. The reader is first provided a basic overview on key mechanisms, targets and therapies in nephrosis while referred to some excellent updates hereon for more detailed information. The broader purpose of this short review, however, is to highlight caveolae/caveolins and caveolar function as central modulators in all the above key processes of nephrosis. Caveolae - little caves in the plasma membrane that are particularly abundant in endothelial cells, amongst others - are now known to be involved not only in endothelial transcytosis (e.g. of albumin) but also in cholesterol homeostasis (LDL-transport) and, importantly, in signal transduction such as insulin signalling and nitric oxide signalling in endothelial function and regulation of vasomotor tone, as well as signalling by growth factor receptors - such as TGF-beta - which may participate in renal scarring. It is suggested that caveolae may represent crucial sites where possible new druggable targets in nephrosis may be found.
van Dokkum
Richard Pe
RP
Department of Clinical Pharmacology, University of Groningen/University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, Netherlands.
Buikema
Hendrik
H
D000419:Albuminuria / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D021941:Caveolae / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology*; D022461:Caveolins / Q000378:metabolism* / Q000502:physiology*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000503:physiopathology; D005355:Fibrosis / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D009401:Nephrosis / Q000188:drug therapy* / Q000503:physiopathology
D000975:Antioxidants; D022461:Caveolins