Preservations of nephrin and synaptopodin by recombinant hepatocyte growth factor in podocytes for the attenuations of foot process injury and albuminuria in nephritic mice.

Abstract

AIM:

Podocytes provide a slit diaphragm to inhibit proteinuria, and nephrin between podocytes functions as a barrier during glomerular filtration. Hepatocyte growth factor (HGF) can improve proteinuria in rodents with various renal injuries, but little is known about the role of HGF in podocyte-based events during glomerulonephritis. In the present study, we examined whether and how nephrin expression is sustained by podocytes during the HGF-mediated attenuation of albuminuria.

METHODS:

Lipopolysaccharide (LPS)-treated mice were used as an animal model of albuminuria. We evaluated the effect of HGF on slit proteins using immunohistochemistry, western blotting and real-time polymerase chain reaction.

RESULTS:

Albuminuria occurred 36 h after LPS treatment in mice. This albuminuria did not involve podocyte loss, but was associated with a decrease in nephrin and its key anchor, synaptopodin. In these processes, c-Met tyrosine phosphorylation, which represented HGF signal activation, occurred in glomerular cells including podocytes. When recombinant HGF was administrated to nephritic mice, c-Met tyrosine phosphorylation became evident in podocytes. The enhancement of the HGF-c-Met signal was associated with increases in nephrin and synaptopodin. An electron microscopic examination revealed that LPS induced the foot process effacement of podocytes, while HGF injections suppressed the foot process injury. Overall, albuminuria was attenuated in the LPS-treated mice after HGF administration.

CONCLUSION:

HGF protects podocytes from a loss of nephrin, at least in part, through maintaining synaptopodin. As a result, HGF was shown to sustain foot process structure, and albuminuria was attenuated under inflammation.

• Authors: Takashi Kato, Shinya Mizuno, Toshikazu Nakamura
• Journal: Nephrology (Carlton, Vic.) (Nephrology (Carlton)) Vol. 16 Issue 3 Pg. 310-8 (Mar 2011) ISSN: 1440-1797 [Electronic] Australia
• PMID: 21342325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.

Chemical References

• HGF protein, human
• Lipopolysaccharides
• Membrane Proteins
• Microfilament Proteins
• Recombinant Proteins
• Synpo protein, mouse
• lipopolysaccharide, Escherichia coli O111 B4
• nephrin
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Albuminuria (chemically induced, genetics, metabolism, pathology, prevention & control)
• Animals
• Blotting, Western
• Disease Models, Animal
• Female
• Glomerulonephritis (chemically induced, genetics, metabolism, pathology, prevention & control)
• Hepatocyte Growth Factor (pharmacology)
• Humans
• Immunohistochemistry
• Lipopolysaccharides
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Microfilament Proteins (metabolism)
• Phosphorylation
• Podocytes (drug effects, metabolism, pathology)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-met (metabolism)
• Recombinant Proteins (metabolism)
• Time Factors