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  • Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by albumin independent of ERK1/2 signaling

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    Author(s)
    Jenkin, Kayte A
    McAinch, Andrew J
    Briffa, Jessica F
    Zhang, Yuan
    Kelly, Darren J
    Pollock, Carol A
    Poronnik, Philip
    Hryciw, Deanne H
    Griffith University Author(s)
    Skelly, Deanne
    Year published
    2013
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    Abstract
    Background: The cannabinoid receptor type 2 (CB2) is reduced in podocytes of animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2 ameliorating albuminuria in animals. As albuminuria also is due to proximal tubule dysfunction, the aim of this study is to investigate tubular expression of CB2 under diabetic conditions in addition to the cell signaling pathways that underlie these changes. Methods: We characterized total CB2 protein in diabetic animals and in Human Kidney 2 (HK2) cells exposed to elevated albumin and glucose, the levels of CB2 mRNA and protein. We also used latrunculin to determine ...
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    Background: The cannabinoid receptor type 2 (CB2) is reduced in podocytes of animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2 ameliorating albuminuria in animals. As albuminuria also is due to proximal tubule dysfunction, the aim of this study is to investigate tubular expression of CB2 under diabetic conditions in addition to the cell signaling pathways that underlie these changes. Methods: We characterized total CB2 protein in diabetic animals and in Human Kidney 2 (HK2) cells exposed to elevated albumin and glucose, the levels of CB2 mRNA and protein. We also used latrunculin to determine if internalization of albumin was required to regulate CB2 levels. Finally, we characterized the levels of active and total AKT, ERK1/2 and p38 in response to albumin. Results: There were no changes to CB2 expression in kidney lysate from diabetic rats. In HK2 cells, expression of CB2 was unaltered following exposure to high glucose. High albumin treatment alone and in combination with high glucose, resulted in a significant reduction in CB2 receptor mRNA expression at 6 and 18 hours. CB2 protein expression was reduced at 6 and 24 hours, in high albumin and in combination with high glucose. Internalization of albumin was required to regulate CB2 levels, and inhibition of ERK1/2, did not rescue the loss of CB2 in response to albumin. Conclusion: We have demonstrated that internalization of albumin is required to reduce CB2 mRNA and protein expression in proximal tubules in vitro. Consequently, altered expression of CB2 in both the podocytes and tubules may contribute to the albuminuria observed in T2DM.
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    Journal Title
    Cellular Physiology and Biochemistry
    Volume
    32
    Issue
    5
    DOI
    https://doi.org/10.1159/000354529
    Copyright Statement
    © The Author(s) 2013. This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
    Subject
    Biochemistry and cell biology
    Medical physiology
    Medical physiology not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/341839
    Collection
    • Journal articles

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