Podocyte proteoglycan synthesis is involved in the development of nephrotic syndrome

A Björnson Granqvist, K Ebefors, MA Saleem, PW Mathieson, B Haraldsson, J Sörensson Nyström

Research output: Contribution to journalArticle (Academic Journal)peer-review

37 Citations (Scopus)

Abstract

Proteoglycans (PGs) are important for the glomerular barrier, for cell signaling, and for the anchorage of cells to the glomerular basement membrane. They are, however, complex macromolecules, and their production has not yet been thoroughly investigated in podocytes. In the present study, we studied the biosynthesis of PGs by highly differentiated human podocytes and in rats. The cells were treated with puromycin aminonucleoside (PAN; a nephrosis-inducing agent), steroids (used as primary treatment for nephrotic syndrome), or both. Analysis was made by TaqMan real-time PCR, Western blotting, and by metabolic labeling with 35S and 3H. We found that podocytes produce versican, syndecan-1, decorin, and biglycan together with the previously known PG syndecan-4, glypican, and perlecan. PAN treatment downregulated the mRNA and the protein expression of both versican (by 24 {+/-} 6%, P <0.01, for mRNA and by 50% for protein) and perlecan (by 14 {+/-} 5%, P <0.05, for mRNA and by 50% for protein). The decreased expression was confirmed by studying the glomerular gene expression in rats treated with PAN during a time course study. In addition, puromycin decreased the expression of enzymes involved in the glycosaminoglycan biosynthesis. Steroid treatment decreased perlecan (by 24 {+/-} 3%, P <0.01) and syndecan-1 expression (by 30 {+/-} 4%, P <0.01) but increased the expression of decorin 2.5-fold. The observed alterations of PG synthesis induced by PAN may lead to decreased glomerular anionic charge and disturbed podocyte morphology, factors that are important for the development of a nephrotic syndrome.
Translated title of the contributionPodocyte proteoglycan synthesis is involved in the development of nephrotic syndrome
Original languageEnglish
Pages (from-to)F722 - F730
Number of pages9
JournalAJP - Renal Physiology
Volume291 (4)
DOIs
Publication statusPublished - Oct 2006

Bibliographical note

Publisher: American Physiological Society

Fingerprint Dive into the research topics of 'Podocyte proteoglycan synthesis is involved in the development of nephrotic syndrome'. Together they form a unique fingerprint.

Cite this