Nephrin in experimental glomerular disease

Pauliina Luimula, Heikki Ahola, Shixuan Wang, Marja Liisa Solin, Petri Aaltonen, Ilkka Tikkanen, Dontscho Kerjaschki, Harry Holthöfer

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Background. The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a rat NPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. Methods. Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. Results. Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80% of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70% from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. Conclusions. Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.

Original languageEnglish (US)
Pages (from-to)1461-1468
Number of pages8
JournalKidney International
Volume58
Issue number4
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Proteinuria
Puromycin Aminonucleoside
Nephrosis
Immunoelectron Microscopy
Messenger RNA
Podocytes
Mercuric Chloride
Indirect Fluorescent Antibody Technique
Fluorescence Microscopy
Reverse Transcription
nephrin
Proteins
Theoretical Models
Down-Regulation
Cell Membrane
Kidney
Polymerase Chain Reaction
Mutation
Antibodies
Genes

Keywords

  • Experimental models
  • Glomerulonephritis
  • Lipid peroxidation
  • Proteinuria
  • Slit diaphragm

ASJC Scopus subject areas

  • Nephrology

Cite this

Luimula, P., Ahola, H., Wang, S., Solin, M. L., Aaltonen, P., Tikkanen, I., ... Holthöfer, H. (2000). Nephrin in experimental glomerular disease. Kidney International, 58(4), 1461-1468. https://doi.org/10.1046/j.1523-1755.2000.00308.x

Nephrin in experimental glomerular disease. / Luimula, Pauliina; Ahola, Heikki; Wang, Shixuan; Solin, Marja Liisa; Aaltonen, Petri; Tikkanen, Ilkka; Kerjaschki, Dontscho; Holthöfer, Harry.

In: Kidney International, Vol. 58, No. 4, 01.01.2000, p. 1461-1468.

Research output: Contribution to journalArticle

Luimula, P, Ahola, H, Wang, S, Solin, ML, Aaltonen, P, Tikkanen, I, Kerjaschki, D & Holthöfer, H 2000, 'Nephrin in experimental glomerular disease', Kidney International, vol. 58, no. 4, pp. 1461-1468. https://doi.org/10.1046/j.1523-1755.2000.00308.x
Luimula P, Ahola H, Wang S, Solin ML, Aaltonen P, Tikkanen I et al. Nephrin in experimental glomerular disease. Kidney International. 2000 Jan 1;58(4):1461-1468. https://doi.org/10.1046/j.1523-1755.2000.00308.x
Luimula, Pauliina ; Ahola, Heikki ; Wang, Shixuan ; Solin, Marja Liisa ; Aaltonen, Petri ; Tikkanen, Ilkka ; Kerjaschki, Dontscho ; Holthöfer, Harry. / Nephrin in experimental glomerular disease. In: Kidney International. 2000 ; Vol. 58, No. 4. pp. 1461-1468.
@article{18f36f8d7480499aa6448be5fa5a3c12,
title = "Nephrin in experimental glomerular disease",
abstract = "Background. The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a rat NPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. Methods. Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. Results. Notably, a 40{\%} down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80{\%} of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70{\%} from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. Conclusions. Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.",
keywords = "Experimental models, Glomerulonephritis, Lipid peroxidation, Proteinuria, Slit diaphragm",
author = "Pauliina Luimula and Heikki Ahola and Shixuan Wang and Solin, {Marja Liisa} and Petri Aaltonen and Ilkka Tikkanen and Dontscho Kerjaschki and Harry Holth{\"o}fer",
year = "2000",
month = "1",
day = "1",
doi = "10.1046/j.1523-1755.2000.00308.x",
language = "English (US)",
volume = "58",
pages = "1461--1468",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Nephrin in experimental glomerular disease

AU - Luimula, Pauliina

AU - Ahola, Heikki

AU - Wang, Shixuan

AU - Solin, Marja Liisa

AU - Aaltonen, Petri

AU - Tikkanen, Ilkka

AU - Kerjaschki, Dontscho

AU - Holthöfer, Harry

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background. The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a rat NPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. Methods. Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. Results. Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80% of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70% from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. Conclusions. Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.

AB - Background. The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a rat NPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. Methods. Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. Results. Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80% of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70% from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. Conclusions. Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.

KW - Experimental models

KW - Glomerulonephritis

KW - Lipid peroxidation

KW - Proteinuria

KW - Slit diaphragm

UR - http://www.scopus.com/inward/record.url?scp=0033807362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033807362&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2000.00308.x

DO - 10.1046/j.1523-1755.2000.00308.x

M3 - Article

C2 - 11012881

AN - SCOPUS:0033807362

VL - 58

SP - 1461

EP - 1468

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -