- Publikační typ
- abstrakt z konference MeSH
Nefrotický syndrom je velmi často přítomen u glomerulonefritid, u diabetické nefropatie a u obezitou indukované glomerulopatie. Všechny tyto stavy spojuje patologie na úrovni podocytu. Podocyt je ústřední buňkou renálního parenchymu a zajišťuje filtraci krve jak strukturálně, tak aktivně regulací vlastností filtrační membrány. V posledních letech je zkoumán stále intenzivněji. Kromě jeho patofyziologie se zkoumají i možnosti jeho diagnostického využití. Přítomnost podocytů v moči koreluje s aktivitou renálních nemocí ústících v nefrotický syndrom. Přitom nefrotický syndrom rezistentní na léčbu hrozí nejen postupnou progresí choroby do konečného selhání ledvin, ale sám o sobě může organizmus vážně poškodit metabolickým rozvratem. Nejvíce prostudované metabolické poruchy u nefrotického syndromu jsou změny v lipidovém spektru, v koagulačních faktorech a změny v renin-angiotenzin-aldosteronovém systému. Ve všech případech se jedná o kompenzační mechanizmy snažící se zajistit homeostázu, která je při protrahovaném průběhu nefrotického syndromu často fatální postižení na podkladě akcelerace rozvoje aterosklerotických změn a následných komplikací. Slibný terapeutický zásah do tohoto stavu představují statiny, především jejich pleiotropní účinky, které by bylo vhodné prozkoumat hlouběji a více využít terapeuticky.
Nephrotic syndrome frequently accompanies glomerulnephritides, including diabetic nephropathy and obestity-induced glomerulopathy, which are marked by pathology at the level of the podocyte. Podocytes are the main cellular component of renal parenchyme facilitating the filtration of blood not only through the inherent structural component they provide the glomerular filtration membrane itself, but also through their active role in regulating it. In the last few years, the pathophysiology of podocytes has been studied extensively as well as their role as a potential diagnostic tool. In light of this, it has been determined that the presence of podocytes in urine correlates to a state of active renal disease leading to nephrotic sydnrome, the consequences of which can be severe. That is to say, in the setting of nephrotic sydrom resistant to treatment, the threat of progressive disease culminating in in end-stage renal failure is high as well the damaging systemic effects of the resulting metabolic disruption. Dyslipidemia, coagulopathy and changes to the renin-angiotensin-aldosterone system are the most studied metabolic disturbances associated with nephrotic syndrome. In all of thesesituations, compensatory mechanisms to restore homeostasis are engaged, which can become dangerously damaged in wake of the accelerateddevelopment of atherosclerotic changes and their ensuing complications, due to a prolonged state of disease. Statins--especially their pleiotropic effects-offer promising therapeautic potential, which needs to be further explored and utilized more extensively in the clinical setting.
- Klíčová slova
- podokalyxin,
- MeSH
- arterioskleróza patologie MeSH
- dyslipidemie patologie MeSH
- lidé MeSH
- nefrotický syndrom * diagnóza patologie terapie MeSH
- podocyty MeSH
- statiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- interakce bylin a léků MeSH
- kouř analýza škodlivé účinky MeSH
- kouření škodlivé účinky MeSH
- nikotin analýza farmakokinetika farmakologie MeSH
- nikotinové receptory MeSH
- pevné částice analýza farmakokinetika farmakologie MeSH
- poruchy vyvolané užíváním tabáku etiologie metabolismus MeSH
- tabák * chemie škodlivé účinky MeSH
- tabákové výrobky normy škodlivé účinky MeSH
- těkavé organické sloučeniny analýza farmakokinetika farmakologie MeSH
BACKGROUND/AIMS: Podocytes are typically cultured on collagen I; however, collagen I is absent from healthy glomerular basement membranes. Erythropoietin (EPO) is thought to protect podocytes in vivo. Here, we studied how various types of extracellular matrix (ECM) proteins and EPO affect podocytes in culture. METHODS: Primary rat podocytes were replated on collagen I, collagen IV, whole ECM extract, laminin, or bare plastic. Cellular adhesion (8 hours after plating), proliferation (5 days, 10 % serum), and resistance to serum deprivation (3 days, 0.5 % serum) were assessed. BrdU incorporation and expression of podocyte-specific markers were employed as measures of cellular proliferation and differentiation, respectively. qPCR was used to verify expression of EPO receptor in cultured podocytes. RESULTS: Cellular adhesion was similar on all ECM proteins and unaffected by EPO. Proliferation was accelerated by laminin and the ECM extract, but the final cell density was similar on all ECM surfaces. Collagen IV supported the serum-deprived cells better than the other ECM proteins. EPO (2-20 ng/ml) improved viability of serum-deprived podocytes on collagen I, collagen IV, and ECM, but not on laminin or bare plastic. The cells expressed mRNA for EPO receptor. CONCLUSION: The physiological ECM proteins are more supportive of primary podocytic cultures compared with collagen I. The protective effects of EPO during serum deprivation are modulated by the cultivation surface.
- MeSH
- barvicí látky MeSH
- erythropoetin farmakologie MeSH
- extracelulární matrix - proteiny fyziologie MeSH
- extracelulární matrix účinky léků metabolismus MeSH
- glomerulus účinky léků MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- podocyty účinky léků MeSH
- primární buněčná kultura MeSH
- receptory erythropoetinu biosyntéza účinky léků MeSH
- rekombinantní proteiny farmakologie MeSH
- tetrazoliové soli MeSH
- thiazoly MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
Podocytes (glomerular visceral epithelial cells) cover the exterior surface of the glomerular capillaries and contribute to the glomerular filtration membrane. Failure of podocyte function is involved in the progression of chronic glomerular disease; accordingly, research interest into podocyte biology is driven by the need for better protection and perhaps recovery of these cells in renal diseases. This review aims at summarizing available techniques for podocyte cell cultures from both the past and present, with special attention to the currently used methods. The establishment of classical primary cultures is based on isolation of glomeruli by differential sieving. Plating of glomeruli onto a collagen surface is followed by an outgrowth of cobblestone-like cells that, after replating, differentiate into arborized, mature podocytes. Currently, the majority of research studies use immortalized podocytic cell lines most often derived from transgenic mice bearing a conditional immortalizing gene. The podocytes can also be collected and cultured from healthy or diseased animal or patient urine. The urinary podocytes obtained from subjects with active glomerulopathies display higher proliferation potential and viability in vitro, perhaps due to disease-induced transdifferentiation. Finally, a list of phenotypic markers useful for identification and characterization of the cultured podocytic elements is provided. Copyright 2007 S. Karger AG, Basel.
- Publikační typ
- abstrakt z konference MeSH
