TY - JOUR
T1 - Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases
AU - Wang, Shi Xuan
AU - Rastaldi, Maria P.
AU - Pätäri, Anu
AU - Ahola, Heikki
AU - Heikkilä, Eija
AU - Holthöfer, Harry
N1 - Funding Information:
Helsinki University Hospital, the Päivikki and Sakari Sohlberg Foundation, the Finnish Foundation of Diabetes Research and the Sigrid Juselius Foundation have supported this work. The expert technical assistance of Mrs. Liisa Pirinen and Mrs. Eeva Häyri is gratefully acknowledged.
PY - 2002
Y1 - 2002
N2 - Background. Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier. Methods. Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies. Results. In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down-regulation in nephrin expression pattern was shown. Conclusions. Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place.
AB - Background. Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier. Methods. Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies. Results. In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down-regulation in nephrin expression pattern was shown. Conclusions. Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place.
KW - Filtration barrier
KW - Glomerular basement membrane
KW - Podocytes
KW - Slit diaphragm
KW - Transmembrane protein
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U2 - 10.1046/j.1523-1755.2002.00114.x
DO - 10.1046/j.1523-1755.2002.00114.x
M3 - Article
C2 - 11786094
AN - SCOPUS:0036147560
SN - 0085-2538
VL - 61
SP - 141
EP - 147
JO - Kidney International
JF - Kidney International
IS - 1
ER -