Abstract
Background: Podocytes play a central role in the formation of the glomerular filtration barrier in the kidney, and their dysfunction has been shown to result in proteinuria. In the present study, we sought to determine the cell-autonomous role of NF-κB, a proinflammatory signaling, within podocytes in proteinuric kidney disease. Methods: Podocyte-specific IκBΔN transgenic (Pod-IκBΔN) mice, in which NF-κB was inhibited specifically in podocytes, were generated by the Cre-loxP technology, and their phenotype was compared with control mice in adriamycin-induced nephropathy. Results: Pod-IκBΔN mice were phenotypically normal and did not exhibit proteinuria at the physiological condition. By the intravenous administration of adriamycin, overt proteinuria appeared in Pod-IκBΔN mice, as well as in control mice. However, of interest, the amount of proteinuria was significantly lower in adriamycin-injected Pod-IκBΔN mice (373 ± 122 mg albumin/g creatinine), compared with adriamycin-injected control mice (992 ± 395 mg albumin/g creatinine). Expression of podocyte-selective slit diaphragm-associated proteins, such as nephrin and synaptopodin, was markedly decreased by adriamycin injection in control mice, whereas the reduction was attenuated in Pod-IκBΔN mice. Adriamycin-induced reduction in synaptopodin expression was also seen in cultured podocytes derived from control mice, but not in those from Pod-IκBΔN mice. Conclusions: Because nephrin and synaptopodin are essential for the maintenance of the slit diaphragm in podocytes, these results suggest that proteinuria in adriamycin-induced nephropathy is caused by the reduction in expression of these proteins. The results also suggest that the NF-κB signalling in podocytes cell-autonomously contributes to proteinuria through the regulation of these proteins.
| Original language | English |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Clinical and Experimental Nephrology |
| DOIs | |
| Publication status | Accepted/In press - 2016 Apr 18 |
Fingerprint
Keywords
- Albuminuria
- Kidney
- NF-κB
- Podocyte
ASJC Scopus subject areas
- Nephrology
- Physiology
- Physiology (medical)
Cite this
Podocyte-specific NF-κB inhibition ameliorates proteinuria in adriamycin-induced nephropathy in mice. / Yamashita, Maho; Yoshida, Tadashi; Suzuki, Sayuri; Honma, Koichiro; Hayashi, Matsuhiko.
In: Clinical and Experimental Nephrology, 18.04.2016, p. 1-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Podocyte-specific NF-κB inhibition ameliorates proteinuria in adriamycin-induced nephropathy in mice
AU - Yamashita, Maho
AU - Yoshida, Tadashi
AU - Suzuki, Sayuri
AU - Honma, Koichiro
AU - Hayashi, Matsuhiko
PY - 2016/4/18
Y1 - 2016/4/18
N2 - Background: Podocytes play a central role in the formation of the glomerular filtration barrier in the kidney, and their dysfunction has been shown to result in proteinuria. In the present study, we sought to determine the cell-autonomous role of NF-κB, a proinflammatory signaling, within podocytes in proteinuric kidney disease. Methods: Podocyte-specific IκBΔN transgenic (Pod-IκBΔN) mice, in which NF-κB was inhibited specifically in podocytes, were generated by the Cre-loxP technology, and their phenotype was compared with control mice in adriamycin-induced nephropathy. Results: Pod-IκBΔN mice were phenotypically normal and did not exhibit proteinuria at the physiological condition. By the intravenous administration of adriamycin, overt proteinuria appeared in Pod-IκBΔN mice, as well as in control mice. However, of interest, the amount of proteinuria was significantly lower in adriamycin-injected Pod-IκBΔN mice (373 ± 122 mg albumin/g creatinine), compared with adriamycin-injected control mice (992 ± 395 mg albumin/g creatinine). Expression of podocyte-selective slit diaphragm-associated proteins, such as nephrin and synaptopodin, was markedly decreased by adriamycin injection in control mice, whereas the reduction was attenuated in Pod-IκBΔN mice. Adriamycin-induced reduction in synaptopodin expression was also seen in cultured podocytes derived from control mice, but not in those from Pod-IκBΔN mice. Conclusions: Because nephrin and synaptopodin are essential for the maintenance of the slit diaphragm in podocytes, these results suggest that proteinuria in adriamycin-induced nephropathy is caused by the reduction in expression of these proteins. The results also suggest that the NF-κB signalling in podocytes cell-autonomously contributes to proteinuria through the regulation of these proteins.
AB - Background: Podocytes play a central role in the formation of the glomerular filtration barrier in the kidney, and their dysfunction has been shown to result in proteinuria. In the present study, we sought to determine the cell-autonomous role of NF-κB, a proinflammatory signaling, within podocytes in proteinuric kidney disease. Methods: Podocyte-specific IκBΔN transgenic (Pod-IκBΔN) mice, in which NF-κB was inhibited specifically in podocytes, were generated by the Cre-loxP technology, and their phenotype was compared with control mice in adriamycin-induced nephropathy. Results: Pod-IκBΔN mice were phenotypically normal and did not exhibit proteinuria at the physiological condition. By the intravenous administration of adriamycin, overt proteinuria appeared in Pod-IκBΔN mice, as well as in control mice. However, of interest, the amount of proteinuria was significantly lower in adriamycin-injected Pod-IκBΔN mice (373 ± 122 mg albumin/g creatinine), compared with adriamycin-injected control mice (992 ± 395 mg albumin/g creatinine). Expression of podocyte-selective slit diaphragm-associated proteins, such as nephrin and synaptopodin, was markedly decreased by adriamycin injection in control mice, whereas the reduction was attenuated in Pod-IκBΔN mice. Adriamycin-induced reduction in synaptopodin expression was also seen in cultured podocytes derived from control mice, but not in those from Pod-IκBΔN mice. Conclusions: Because nephrin and synaptopodin are essential for the maintenance of the slit diaphragm in podocytes, these results suggest that proteinuria in adriamycin-induced nephropathy is caused by the reduction in expression of these proteins. The results also suggest that the NF-κB signalling in podocytes cell-autonomously contributes to proteinuria through the regulation of these proteins.
KW - Albuminuria
KW - Kidney
KW - NF-κB
KW - Podocyte
UR - http://www.scopus.com/inward/record.url?scp=84964334362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964334362&partnerID=8YFLogxK
U2 - 10.1007/s10157-016-1268-6
DO - 10.1007/s10157-016-1268-6
M3 - Article
C2 - 27089875
AN - SCOPUS:84964334362
SP - 1
EP - 11
JO - Clinical and Experimental Nephrology
JF - Clinical and Experimental Nephrology
SN - 1342-1751
ER -