Purinergic receptor (P2X7) activation reduces cell–cell adhesion between tubular epithelial cells of the proximal kidney

Siamantouras, Eleftherios and Price, Gareth and Potter, Joe and Hills, Claire and Squires, Paul (2019) Purinergic receptor (P2X7) activation reduces cell–cell adhesion between tubular epithelial cells of the proximal kidney. Nanomedicine: Nanotechnology, Biology and Medicine, 22 . ISSN 1549-9634

Full content URL: https://doi.org/10.1016/j.nano.2019.102108

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Purinergic receptor (P2X7) activation reduces cell–cell adhesion between tubular epithelial cells of the proximal kidney
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Abstract

Loss of epithelial (E)-cadherin mediated cell-cell adhesion impairs gap junction formation and facilitates hemichannel-mediated ATP release in the diabetic kidney. Linked to inflammation and fibrosis, we hypothesized that local increases in inter-cellular ATP activate P2X7 receptors on neighbouring epithelial cells of the proximal tubule, to further impair cell-cell adhesion and ultimately exacerbate tubular injury. Immunoblotting confirmed changes in E-cadherin expression in human kidney cells treated with non-hydrolysable ATPγS ± the P2X7 antagonist, A438079. Atomic force microscopy based single-cell force spectroscopy quantified maximum unbinding force, tether rupture events, and work of detachment. Confocal microscopy assessed cytoskeletal reorganisation. Our studies confirmed that ATPγS downregulated E-cadherin expression in proximal kidney cells, loss of which was paralleled by a reduction in intercellular ligation forces, decreased tether rupture events and cytoskeletal remodelling. Co-incubation with A438079 restored loss of adhesion, suggesting that elevated extracellular ATP mediates tubular injury through P2X7 induced loss of E-cadherin mediated adhesion.

Keywords:Kidney, Adherens Junction, Cell adhesion, ATP, P2X7, AFM-SCFS
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
H Engineering > H673 Bioengineering
B Subjects allied to Medicine > B120 Physiology
C Biological Sciences > C130 Cell Biology
Divisions:College of Science > School of Life Sciences
ID Code:38091
Deposited On:01 Nov 2019 09:09

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