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Published VersionCC BY-NC V3.0, Open
Journal article
Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by albumin independent of ERK1/2 signaling
Cellular Physiology and Biochemistry, Vol.32(5), pp.1309-1319
2013
PMID: 24280624
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 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.
Details
- Title
- Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by albumin independent of ERK1/2 signaling
- Authors
- Kayte A Jenkin - Victoria School of ManagementAndrew J McAinch (Author) - Victoria UniversityJessica F Briffa (Author) - Victoria UniversityYuan Zhang (Author) - St Vincent's Hospital MelbourneDarren J Kelly (Author) - St Vincent's Hospital MelbourneCarol A Pollock (Author) - The University of SydneyPhilip Poronnik (Author) - The University of SydneyDeanne H Hryciw (Corresponding Author) - The University of Melbourne
- Publication details
- Cellular Physiology and Biochemistry, Vol.32(5), pp.1309-1319
- Publisher
- Cellular Physiology and Biochemistry
- Date published
- 2013
- DOI
- 10.1159/000354529
- ISSN
- 1421-9778; 1015-8987
- PMID
- 24280624
- Copyright note
- © 2013 S. Karger AG, Basel. This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 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.
- Grant note
- KAJ is supported by an Australian Postgraduate Award (APA) scholarship. AJM is supported by an Australian government collaborative research network (CRN) program. This work was supported by a grant from the Allen Foundation (2011.385).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187226502621
- Output Type
- Journal article
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