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

Siamantouras, Eleftherios, Price, Gareth, Potter, Joe , 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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