Podocytes and novel therapeutic targets for nephrotic syndrome

Key Findings & Data:Proteins that are associated with the slit diaphragm (for example, nephrin, podocin, α-actinin-4, the adaptor protein CD2AP, and TRPC6), and those that anchor the foot processes to the glomerular basal membrane (GBM) (for example, α3β1 integrin, integrin-linked kinase (ILK), and the tetraspanin CD151), are connected to the actin cytoskeleton, which has an important role in the prevention of proteinuria.

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Conclusion & Impact:Understanding of the mechanisms of the podocyte injury will probably reveal novel therapeutic targets for proteinuria.

🔬Design:Research Article

📍Scope:Comprehensive Sample

⚙️Variables:Proteinüri · Anjiyotensin dönüştürücü enzim inhibitörleri · Nefrotik sendrom

Abstract

The podocytes are highly differentiated cells. Proteins that are associated with the slit diaphragm (for example, nephrin, podocin, α-actinin-4, the adaptor protein CD2AP, and TRPC6), and those that anchor the foot processes to the glomerular basal membrane (GBM) (for example, α3β1 integrin, integrin-linked kinase (ILK), and the tetraspanin CD151), are connected to the actin cytoskeleton, which has an important role in the prevention of proteinuria. Podocyte and slit diaphragm injury is a hallmark of glomerular disease, which is generally displayed by the rearrangement of the podocyte slit diaphragm and the actin cytoskeleton. Proteinuria is often accompanied by a cytopathological change in the glomerulus that is referred to as effacement of the podocyte foot processes. Podocyte-associated genetic defects result in proteinuria and progression to focal segmental glomerulosclerosis (FSGS). Understanding of the mechanisms of the podocyte injury will probably reveal novel therapeutic targets for proteinuria.

Özet

Podositler yüksek diferansiyasyon gösteren hücrelerdir. Podositlerin belki de en önemli komponentleri olan slit diyafram ve onunla ilişkili proteinler (mesela; nefrin, podosin, α3β1 integrin, alfa-aktinin-4 (ACTN4), adaptör protein CD2AP ve TRCP6) ile ayaksı çıkıntıları altındaki glomerüler bazal membrana bağlayan proteinler (mese la; α3β1 integrin, integrin-linked kinaz (ILK) ve tetraspanin CD151 ) podositlerdeki aktin-hücre iskeleti ile bağ kurar lar ve proteinürinin önlenmesinde kritik rol oynarlar. Genellikle podosit slit diyafram ve aktin-hücre iskeleti üzerinde sergilenen podosit hasarı, glomerüler hastalık ların karakteristik özelliğidir. Proteinüri, sık olarak podosit ayaksı çıkıntılarda silinme ve büzüşmelerle karakterize glomerülde ortaya çıkan sitopatolojik değişikliklerle bir liktedir. Podosit ilişkili genetik defektler proteinüri ve fokal segmental glomeruloskleroz (FSGS) ile sonuçlanır lar. Podosit hasar mekanizmalarının iyi anlaşılması, proteinürinin tedavisinde de yeni gelişmeleri beraberinde getirecektir.

Keywords

Proteinüri Anjiyotensin dönüştürücü enzim inhibitörleri Nefrotik sendrom Podosit Proteinuria Angiotensin-Converting Enzyme Inhibitors Nephrotic Syndrome Podocytes

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Cite This Article

DENİZLİ, N., KIRAÇ, Y., GÜCÜN, M., DEMİRCİ, R., DURANAY, M. (2012). Podocytes and novel therapeutic targets for nephrotic syndrome. Yeni Tıp Dergisi, Cilt: 29 - Sayı: 1, 12–18. https://ajindex.com/articles/338221

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References (14)

Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med 2006;354(13):1387– 401
Oh J, Reiser J, Mundel P. Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome. Pediatr Nephrol 2004;19(2):130–7
Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, et al. Positionally cloned gene for a novel glomerular protein-nephrin-is mutated in congenital nephrotic syndrome. Mol Cell 1998;1(4): 575-82
Cohen CD, Klingenhoff A, Boucherot A, Nitsche A, Henger A, Brunner B, et al. Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins. Proc Natl Acad Sci U S A 2006;103(15):5682-7
Schlöndorff J, Del Camino D, Carrasquillo R, Lacey V, Pollak MR. TRPC6 mutations associated with focal segmental glomerulosclerosis cause constitutive activation of NFAT-dependent transcription. Am J Physiol Cell Physiol 2009;296(3):C 558-69
Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 2005;308 (5729):1801–4
Reiser J, Polu KR, Moller CC, Kenlan P, Altintas MM, Wei C, et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 2005;37(7):739–44
Orikasa M, Matsui K, Oite T, Shimizu F. Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody. J Immunol 1988;141(3):807-14
Chiang CK, Inagi R. Glomerular diseases: genetic causes and future therapeutics. Nat Rev Nephrol 2010;6(9):539-54
Mundel P, Reiser J. Proteinuria: an enzymatic disease of the podocyte? Kidney Int 2010;77(7):571-80
Schlondorff J. Nephrin AKTs on actin: The slit diaphragm-actin cytoskeleton signaling network expands. Kidney Int 2008;73(5):524-6
Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, et al. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 2003;23(14): 4917–28
Jones N, Blasutig IM, Eremina V, Ruston JM, Bladt F, Li H, et al. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature 2006;440(7085):818–23
Fuchshuber A, Jean G, Gribouval O, Gubler MC, Broyer M, Beckmann JS, et al. Mapping a gene (SRN1) to chromosome 1q25–q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosoma