TGF-beta 1 mediates glucose-evoked up-regulation of connexin-43 cell-to-cell communication in HCD-cells

Hills, C. E., Bland, R., Bennett, J. , Ronco, P. M. and Squires, P. E. (2009) TGF-beta 1 mediates glucose-evoked up-regulation of connexin-43 cell-to-cell communication in HCD-cells. Cellular Physiology and Biochemistry, 24 (3-4). pp. 177-186. ISSN 1015-8987

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Background/Aims: In the current study we examined if the multifunctional cytokine TGF-beta 1 mediated glucose-evoked increases in connexin-43(Cx43)-mediated intercellular communication in cells of the human collecting duct (HCD). Methods: RT-PCR and western blot analysis were used to confirm mRNA and protein expression of TGF-beta 1 and Cx43 in HCD-cells. The effect of TGF-beta 1 and high glucose (25mM) on Cx43 protein expression, cytoskeletal organisation and cell-cell communication was determined in the presence/absence of TGF-beta 1 specific immuno-neutralising antibodies. Functional cell-cell communication was determined using Ca2+-microfluorimetry. Results: At 24hrs, high glucose (25mM) significantly increased Cx43 mRNA and protein expression. Changes were mimicked by TGF-beta 1 (2ng/ml) at low glucose (5mM). Both high glucose and TGF-beta 1 mediated changes were completely reversed by a pan-specific immuno-neutralising antibody to TGF-beta. Furthermore, high glucose-evoked changes were inhibited by a TGF-beta 1-specific monoclonal antibody. Mannitol (25mM), an osmotic control for high glucose, failed to alter Cx43 expression. TGF-beta 1 evoked changes in Cx43 expression were biphasic. An early (4-8hr) transient decrease in expression was followed by an increase in protein expression (12-24hr). The decrease in Cx43 expression was paralleled by a transient reorganisation of the actin cytoskeleton, whilst increased Cx43 expression at 24hrs coincided with a TGF-beta 1 specific increase in touch-evoked transmission of Ca2+-signals between coupled cells. Conclusions: High glucose evoked a TGF-beta 1 mediated increase in Cx43 expression and gap-junction mediated cell-cell communication in HCD-cells. These changes may maintain epithelial integrity of the collecting duct following hyperglycaemic assault as observed in diabetes. Copyright (C) 2009 S. Karger AG, Basel

Keywords:Human collecting duct
Subjects:Library of Congress Subject Areas > Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Areas > Q Science > QP Physiology
Divisions:College of Science > School of Life Sciences
ID Code:14070
Deposited On:20 Apr 2011 12:58

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