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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| 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. |
| format | Article |
| id | doaj-art-f8c63faa3d0a4261bf27e7d411616e63 |
| institution | Kabale University |
| issn | 2090-214X 2090-2158 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| 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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