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Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction
Joint Authors
Ejima, Yutaka
Yamauchi, Masanori
Saito, Kazutomo
Abe, Nozomu
Mushiake, Hajime
Toyama, Hiroaki
Kazama, Itsuro
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-07
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Background.
Delayed rectifier K+-channel, Kv1.3, is most predominantly expressed in T-lymphocytes and macrophages.
In such leukocytes, Kv1.3-channels play pivotal roles in the activation and proliferation of cells, promoting cellular immunity.
Since leukocyte-derived cytokines stimulate fibroblasts to produce collagen fibers in inflamed kidneys, Kv1.3-channels expressed in leukocytes would contribute to the progression of tubulointerstitial renal fibrosis.
Methods.
Male Sprague-Dawley rats that underwent unilateral ureteral obstruction (UUO) were used at 1, 2, or 3 weeks after the operation.
We examined the histological features of the kidneys and the leukocyte expression of Kv1.3-channels.
We also examined the therapeutic effects of a selective channel inhibitor, margatoxin, on the progression of renal fibrosis and the proliferation of leukocytes within the cortical interstitium.
Results.
In rat kidneys with UUO, progression of renal fibrosis and the infiltration of leukocytes became most prominent at 3 weeks after the operation, when Kv1.3-channels were overexpressed in proliferating leukocytes.
In the cortical interstitium of margatoxin-treated UUO rat kidneys, immunohistochemistry revealed reduced expression of fibrosis markers.
Additionally, margatoxin significantly decreased the numbers of leukocytes and suppressed their proliferation.
Conclusions.
This study clearly demonstrated that the numbers of T-lymphocytes and macrophages were markedly increased in UUO rat kidneys with longer postobstructive days.
The overexpression of Kv1.3-channels in leukocytes was thought to be responsible for the proliferation of these cells and the progression of renal fibrosis.
This study strongly suggested the therapeutic usefulness of targeting lymphocyte Kv1.3-channels in the treatment of renal fibrosis.
American Psychological Association (APA)
Abe, Nozomu& Toyama, Hiroaki& Saito, Kazutomo& Ejima, Yutaka& Yamauchi, Masanori& Mushiake, Hajime…[et al.]. 2019. Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction. BioMed Research International،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1127380
Modern Language Association (MLA)
Abe, Nozomu…[et al.]. Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction. BioMed Research International No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1127380
American Medical Association (AMA)
Abe, Nozomu& Toyama, Hiroaki& Saito, Kazutomo& Ejima, Yutaka& Yamauchi, Masanori& Mushiake, Hajime…[et al.]. Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction. BioMed Research International. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1127380
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1127380