Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure

Leukocytes, such as lymphocytes and macrophages, predominantly express delayed rectifier K+ channels (Kv1.3), and the channels play crucial roles in the activation and proliferation of the cells. Since lymphocytes are activated in patients with end-stage renal disease (ESRD), the channels expressed...

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Main Authors: Itsuro Kazama, Yoshio Maruyama, Yasuhiro Endo, Hiroaki Toyama, Yutaka Ejima, Mitsunobu Matsubara, Shin Kurosawa
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:International Journal of Nephrology
Online Access:http://dx.doi.org/10.1155/2012/581581
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author Itsuro Kazama
Yoshio Maruyama
Yasuhiro Endo
Hiroaki Toyama
Yutaka Ejima
Mitsunobu Matsubara
Shin Kurosawa
author_facet Itsuro Kazama
Yoshio Maruyama
Yasuhiro Endo
Hiroaki Toyama
Yutaka Ejima
Mitsunobu Matsubara
Shin Kurosawa
author_sort Itsuro Kazama
collection DOAJ
description Leukocytes, such as lymphocytes and macrophages, predominantly express delayed rectifier K+ channels (Kv1.3), and the channels play crucial roles in the activation and proliferation of the cells. Since lymphocytes are activated in patients with end-stage renal disease (ESRD), the channels expressed in those cells would contribute to the progression of renal fibrosis in advanced-stage chronic renal failure (CRF). In the present study, using a rat model with advanced CRF that underwent 5/6 nephrectomy followed by a 14-week recovery period, we examined the histopathological features of the kidneys and the leukocyte expression of Kv1.3-channels and cell cycle markers. Age-matched sham-operated rats were used as controls. In the cortical interstitium of advanced CRF rat kidneys, leukocytes proliferated in situ and overexpressed Kv1.3 channel protein in their cytoplasm. Treatment with margatoxin, a selective Kv1.3-channel inhibitor, significantly suppressed the number of leukocytes and the progression of renal fibrosis with a significant decrease in the cortical cell cycle marker expression. This study demonstrated for the first time that the number of leukocytes was dramatically increased in rat kidneys with advanced CRF. The overexpression of Kv1.3 channels in the leukocytes was thought to contribute to the progression of renal fibrosis by stimulating cell cycling and promoting cellular proliferation.
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publishDate 2012-01-01
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series International Journal of Nephrology
spelling doaj-art-f8c63faa3d0a4261bf27e7d411616e632025-02-03T01:25:20ZengWileyInternational Journal of Nephrology2090-214X2090-21582012-01-01201210.1155/2012/581581581581Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal FailureItsuro Kazama0Yoshio Maruyama1Yasuhiro Endo2Hiroaki Toyama3Yutaka Ejima4Mitsunobu Matsubara5Shin Kurosawa6Department of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Anesthesiology, Tohoku University Hospital, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, JapanDepartment of Anesthesiology, Tohoku University Hospital, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, JapanDepartment of Anesthesiology, Tohoku University Hospital, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, JapanDivision of Molecular Medicine, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Anesthesiology, Tohoku University Hospital, Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, JapanLeukocytes, such as lymphocytes and macrophages, predominantly express delayed rectifier K+ channels (Kv1.3), and the channels play crucial roles in the activation and proliferation of the cells. Since lymphocytes are activated in patients with end-stage renal disease (ESRD), the channels expressed in those cells would contribute to the progression of renal fibrosis in advanced-stage chronic renal failure (CRF). In the present study, using a rat model with advanced CRF that underwent 5/6 nephrectomy followed by a 14-week recovery period, we examined the histopathological features of the kidneys and the leukocyte expression of Kv1.3-channels and cell cycle markers. Age-matched sham-operated rats were used as controls. In the cortical interstitium of advanced CRF rat kidneys, leukocytes proliferated in situ and overexpressed Kv1.3 channel protein in their cytoplasm. Treatment with margatoxin, a selective Kv1.3-channel inhibitor, significantly suppressed the number of leukocytes and the progression of renal fibrosis with a significant decrease in the cortical cell cycle marker expression. This study demonstrated for the first time that the number of leukocytes was dramatically increased in rat kidneys with advanced CRF. The overexpression of Kv1.3 channels in the leukocytes was thought to contribute to the progression of renal fibrosis by stimulating cell cycling and promoting cellular proliferation.http://dx.doi.org/10.1155/2012/581581
spellingShingle Itsuro Kazama
Yoshio Maruyama
Yasuhiro Endo
Hiroaki Toyama
Yutaka Ejima
Mitsunobu Matsubara
Shin Kurosawa
Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
International Journal of Nephrology
title Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
title_full Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
title_fullStr Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
title_full_unstemmed Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
title_short Overexpression of Delayed Rectifier K+ Channels Promotes In situ Proliferation of Leukocytes in Rat Kidneys with Advanced Chronic Renal Failure
title_sort overexpression of delayed rectifier k channels promotes in situ proliferation of leukocytes in rat kidneys with advanced chronic renal failure
url http://dx.doi.org/10.1155/2012/581581
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