Glomerular filtration is normal in the absence of both agrin and perlecan-heparan sulfate from the glomerular basement membrane

被引:77
作者
Goldberg, Seth [1 ]
Harvey, Scott J. [1 ]
Cunningham, Jeanette [1 ]
Tryggvason, Karl [2 ]
Miner, Jeffrey H. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA
[2] Karolinska Inst, Div Matrix Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
基金
英国医学研究理事会;
关键词
charge selectivity; Ficoll; glomerular basement membrane; glomerular filtration; perlecan; DENSITY-LIPOPROTEIN RECEPTOR; CELL-ADHESION MOLECULES; ANIONIC SITES; CHARGE SELECTIVITY; CAPILLARY WALL; GLYCOSAMINOGLYCANS; PROTEOGLYCAN; PODOCALYXIN; EXPRESSION; PERMSELECTIVITY;
D O I
10.1093/ndt/gfn758
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Methods. Here we studied the nature of the glomerular filtration barrier to albumin in mice lacking the HS chains of perlecan either alone or in combination with podocyte-specific loss of agrin. Results. The results show significant reductions in anionic sites within the GBM in perlecan-HS and in perlecan-HS/agrin double mutants. Podocyte and overall glomerular architecture were normal, and renal function was normal up to 15 months of age with no measurable proteinuria. Moreover, excretion of a negatively charged Ficoll tracer was unchanged as compared to control mice. Conclusions. These findings cast further doubt upon a critical role for the GBM in charge selectivity.
引用
收藏
页码:2044 / 2051
页数:8
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