This study was undertaken to test the hypothesis that altered podocyte slit protein nephrin distribution is associated with disturbed polarity protein expressions in podocytes from preeclampsia (PE). We examined expressions and distributions of nephrin, podoplanin, polarity protein partitioning defective-3 (PARD-3), and PARD-6 in podocytes from PE. Podocyte cell line (AB 8/13 cells) was used as control. Podocytes were found in all severe PE cases. In contrast, no podocyte was found in the samples from normal pregnancies and mild PE. Compared to control cells, nephrin, PARD-3 and PARD-6 expressions were reduced or lost in podocytes from severe PE. Podoplanin was expressed in podocyte surface membrane on control cells but reduced in podocytes from PE. These findings indicate that loss of slit protein nephrin and polarity protein PARD-3 and PARD-6 on foot processes could explain for podocyte detachment from glomerular basement membrane and lead to podocyte shedding in PE.
GaberLWLindheimerMD. Pathology of the kidney, liver, and brain. In: LindheimerMDRobertsJMCunninghamFG Chesley'sHypertensive Disorder in Pregnancy. 2nd ed.Appleton & Lange, Stanford, Connecticut. 1999:231–262.
2.
GarovicVDWagnerSJTurnerSTUrinary podocyte excretion as a marker for preeclampsia. In: Am J Obstet Gynecol.2007;196(4):320.e321–327.
3.
GarovicVDWagnerSJPetrovicLM. Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant. 2007;22(4):1136–1143.
4.
ZhaoSGuXGroomeLJWangY. Decreased nephrin and GLEPP-1, but increased VEGF, Flt-1, and nitrotyrosine, expressions in kidney tissue sections from women with preeclampsia. Reprod Sci. 2009;16(10):970–979.
5.
VogelmannSUNelsonWJMyersBDLemleyKV. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol. 2003;285(1):F40–F48.
6.
SaleemMAO'HareMJReiserJ. A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol. 2002;13(3):630–638.
7.
DoublierSSalvidioGLupiaE. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Diabetes. 2003;52(4):1023–1030.
8.
PatrakkaJTryggvasonK. Molecular make-up of the glomerular filtration barrier. Biochem Biophys Res Commun. 2010;386(1):164–169.
9.
WelshGISaleemMA. Nephrin-signature molecule of the glomerular podocyte?J Pathol. 2010;220(3):328–337.
10.
HuberTBBenzingT. The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens. 2005;14(3):211–214.
11.
HaritaYKuriharaHKosakoH. Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1. J Biol Chem. 2009;284(13):8951–8962.
12.
ShihNYLiJCotranRMundelPMinerJHShawAS. CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. Am J Pathol. 2001;159(6):2303–2308.
13.
JonesNBlasutigIMEreminaV. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature. 2006;440(7085):818–823.
14.
FaulCAsanumaKYanagida-AsanumaEKimKMundelP. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol. 2007;17(9):428–437.
15.
KestiläMLenkkeriUMännikköM. Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. Mol Cell. 1998;1(4):575–582.
16.
PutaalaHSoininenRKilpeläinenPWartiovaaraJTryggvasonK. The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet. 2001;10(1):1–8.
17.
ShanklandSJ. The podocyte's response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 2006;69(12):2131–2147.
18.
AitaKEtohMHamadaHYokoyamaCTakahashiASuzukiTHaraMNagataM. Acute and transient podocyte loss and proteinuria in preeclampsia. Nephron Clin Pract. 2009;112(2):c65–c70.
19.
HartlebenBSchweizerHLübbenP. Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity. J Biol Chem. 2008;283(34):23033–23038.
20.
SkoberneAKoniecznyASchifferM. Glomerular epithelial cells in the urine: what has to be done to make them worthwhile?Am J Physiol Renal Physiol. 2009;296(2):F230–F241.
21.
BariétyJBrunevalPHillGSMandetCJacquotCMeyrA. Transdifferentiation of epithelial glomerular cells. J Am Soc Nephrol. 2003;14(suppl 1):S42–S47.
22.
NagataMHoritaSShuYShibataSHattoriMItoKWatanabeT. Phenotypic characteristics and cyclin-dependent kinase inhibitors repression in hyperplastic epithelial pathology in idiopathic focal segmental glomerulosclerosis. Lab Invest. 2000;80(6):869–880.
23.
BariétyJNochyDMandetCJacquotCGlotzDMeyrierA. Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int. 1998;53(4):918–925.
24.
HenaoDESaleemMACadavidAP. Glomerular disturbances in preeclampsia: disruption between glomerular endothelium and podocyte symbiosis. Hypertens Pregnancy. 2010;29(1):10–20.
25.
HenaoDEAriasLFMathiesonPW. Preeclamptic sera directly induce slit-diaphragm protein redistribution and alter podocyte barrier-forming capacity. Nephron Exp Nephrol. 2008;110(3):e73–e81.
26.
CollinoFBussolatiBGerbaudoE. Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells. Am J Physiol Renal Physiol. 2008;294(5):F1185–1194.
27.
HenaoDEMathiesonPWSaleemMABuenoJCCadavidA. A novel renal perspective of preeclampsia: a look from the podocyte. Nephrol Dial Transplant. 2007;22(5):1477.
