Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis
Background/Aims: The transmembrane proteins Neph1 and nephrin form a complex in the slit diaphragm (SD) of podocytes. As recent studies indicate an involvement of this complex in the polymerization of the actin cytoskeleton and proteinuria, we wanted to study the subcellular localization of Neph1 in...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Karger Publishers
2014-09-01
|
Series: | Nephron Extra |
Subjects: | |
Online Access: | http://www.karger.com/Article/FullText/365091 |
id |
doaj-bed34355f19e4568a2b87a99d6ffbc23 |
---|---|
record_format |
Article |
spelling |
doaj-bed34355f19e4568a2b87a99d6ffbc232020-11-24T22:55:10ZengKarger PublishersNephron Extra1664-55292014-09-014314615410.1159/000365091365091Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside NephrosisJenny HulkkoJaakko PatrakkaMark LalKarl TryggvasonKjell HultenbyAnnika WernersonBackground/Aims: The transmembrane proteins Neph1 and nephrin form a complex in the slit diaphragm (SD) of podocytes. As recent studies indicate an involvement of this complex in the polymerization of the actin cytoskeleton and proteinuria, we wanted to study the subcellular localization of Neph1 in the normal human kidney and its expression in focal segmental glomerulosclerosis (FSGS), minimal change nephrotic syndrome (MCNS), and the corresponding experimental models of Adriamycin-induced nephropathy (ADR) and puromycin aminonucleoside nephrosis (PAN). All these disorders are characterized by substantial foot process effacement (FPE) and proteinuria. Materials and Methods: Kidney biopsies from patients with primary FSGS (perihilar type) and MCNS were compared to normal renal tissue. Mouse and rat kidney cortices from days 7 and 14 after Adriamycin injection and days 2 and 4 after puromycin aminonucleoside injection, respectively, were compared to control mouse and rat kidney. Polyclonal antibodies against Neph1 and nephrin were used for immunoelectron microscopy, and semiquantification was performed. Results: We localized Neph1 mainly to, and in close proximity to, the SD. Double staining of Neph1 and nephrin showed the proteins to be in close connection in the SD. The total amount of Neph1 in the podocytes was significantly reduced in FSGS, MCNS, ADR, and PAN. The reduction of Neph1 was also seen in areas with and without FPE. Nephrin was reduced in MCNS and PAN but unchanged in FSGS. Conclusion: With nephrin (but not Neph1) unchanged in FSGS, there might be a disruption of the complex and an involvement of Neph1 in its pathogenesis.http://www.karger.com/Article/FullText/365091Adriamycin-induced nephropathyPuromycin aminonucleoside nephrosisNeph1Focal segmental glomerulosclerosisMinimal change nephrotic syndrome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jenny Hulkko Jaakko Patrakka Mark Lal Karl Tryggvason Kjell Hultenby Annika Wernerson |
spellingShingle |
Jenny Hulkko Jaakko Patrakka Mark Lal Karl Tryggvason Kjell Hultenby Annika Wernerson Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis Nephron Extra Adriamycin-induced nephropathy Puromycin aminonucleoside nephrosis Neph1 Focal segmental glomerulosclerosis Minimal change nephrotic syndrome |
author_facet |
Jenny Hulkko Jaakko Patrakka Mark Lal Karl Tryggvason Kjell Hultenby Annika Wernerson |
author_sort |
Jenny Hulkko |
title |
Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis |
title_short |
Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis |
title_full |
Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis |
title_fullStr |
Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis |
title_full_unstemmed |
Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis |
title_sort |
neph1 is reduced in primary focal segmental glomerulosclerosis, minimal change nephrotic syndrome, and corresponding experimental animal models of adriamycin-induced nephropathy and puromycin aminonucleoside nephrosis |
publisher |
Karger Publishers |
series |
Nephron Extra |
issn |
1664-5529 |
publishDate |
2014-09-01 |
description |
Background/Aims: The transmembrane proteins Neph1 and nephrin form a complex in the slit diaphragm (SD) of podocytes. As recent studies indicate an involvement of this complex in the polymerization of the actin cytoskeleton and proteinuria, we wanted to study the subcellular localization of Neph1 in the normal human kidney and its expression in focal segmental glomerulosclerosis (FSGS), minimal change nephrotic syndrome (MCNS), and the corresponding experimental models of Adriamycin-induced nephropathy (ADR) and puromycin aminonucleoside nephrosis (PAN). All these disorders are characterized by substantial foot process effacement (FPE) and proteinuria. Materials and Methods: Kidney biopsies from patients with primary FSGS (perihilar type) and MCNS were compared to normal renal tissue. Mouse and rat kidney cortices from days 7 and 14 after Adriamycin injection and days 2 and 4 after puromycin aminonucleoside injection, respectively, were compared to control mouse and rat kidney. Polyclonal antibodies against Neph1 and nephrin were used for immunoelectron microscopy, and semiquantification was performed. Results: We localized Neph1 mainly to, and in close proximity to, the SD. Double staining of Neph1 and nephrin showed the proteins to be in close connection in the SD. The total amount of Neph1 in the podocytes was significantly reduced in FSGS, MCNS, ADR, and PAN. The reduction of Neph1 was also seen in areas with and without FPE. Nephrin was reduced in MCNS and PAN but unchanged in FSGS. Conclusion: With nephrin (but not Neph1) unchanged in FSGS, there might be a disruption of the complex and an involvement of Neph1 in its pathogenesis. |
topic |
Adriamycin-induced nephropathy Puromycin aminonucleoside nephrosis Neph1 Focal segmental glomerulosclerosis Minimal change nephrotic syndrome |
url |
http://www.karger.com/Article/FullText/365091 |
work_keys_str_mv |
AT jennyhulkko neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis AT jaakkopatrakka neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis AT marklal neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis AT karltryggvason neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis AT kjellhultenby neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis AT annikawernerson neph1isreducedinprimaryfocalsegmentalglomerulosclerosisminimalchangenephroticsyndromeandcorrespondingexperimentalanimalmodelsofadriamycininducednephropathyandpuromycinaminonucleosidenephrosis |
_version_ |
1725657639930560512 |