Expression of Podocyte-Associated Molecules in Acquired Human Kidney Diseases

Abstract

Abstract. Proteinuria is a poorly understood feature of many acquired renal diseases. Recent studies concerning congenital nephrotic syndromes and findings in genetically modified mice have demonstrated that podocyte molecules make a pivotal contribution to the maintenance of the selective filtration barrier of the normal glomerulus. However, it is unclear what role podocyte molecules play in proteinuria of acquired renal diseases. This study investigated the mRNA and protein expression of several podocyte-associated molecules in acquired renal diseases. Forty-eight patients with various renal diseases were studied, including minimal change nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, and diabetic nephropathy, together with 13 kidneys with normal glomerular function. Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays. Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot process width, and to clinical parameters. In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls. The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r ϭ Ϫ0.443, P Ͻ 0.05), whereas it was positively correlated with podoplanin mRNA levels (r ϭ 0.468, P Ͻ 0.05) and proteinuria (r ϭ 0.585, P ϭ 0.001). In the diseases studied, the decrease of slit diaphragm proteins was related to the effacement of foot processes and coincided with a rise of the levels of the corresponding mRNA transcripts. This suggests that the alterations in the expression of podocyte-associated molecules represent a compensatory reaction of the podocyte that results from damage associated with proteinuria.

Defining cell-type specificity at the transcriptional level in human disease

“…Mutations in such genes often do not cause early embryonic lethality but rather manifest disease at the time when the function of these genes becomes critical for a specific tissue and subsequently for organismal survival (D'Agati 2008). In acquired disease like diabetes or hypertension, the vulnerability of a specific organ to the systemic disease is defined by the expression of tissue-specific genes (Doublier et al 2003;Koop et al 2003;Woroniecka et al 2011). Defining cell-lineage-specific transcripts therefore has immediate clinical implications for such cell lineages.…”

Study of the morphologic variants of focal segmental glomerulosclerosis: a Brazilian report

“…From an etiological standpoint, FSGS may be associated with a variety of conditions, including viral infections (human immunodeficiency virus [HIV], simian virus 40 [SV40] , parvovirus B19), several drugs (heroin, pamidronate, interferon), adaptive to hyperfiltration (as in hypertension, obesity, and sickle-cell anemia), and genetic disorders (familiar forms), and may be idiopathic (11) . Podocyte injury is the core pathophysiological event of FSGS and some studies have found anomalous expression of podocyte proteins in FSGS (2,10,16) Table and Figure). Studies of these variants demonstrated correlation with distinct clinical characteristics and prognostic and therapeutic implications (4,18) .…”

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

“…These genomic studies lead to the determination of a molecular topology for SD, required for maintaining the homeostasis of podocytespodocytes [21]. Notably, the decreases of SD-related molecules (such as podocin and CD2AP) are observed in many types of CKD, regardless of the primary etiology [1,19].…”