Purinergic receptor (P2X7) activation reduces cell-cell adhesion between tubular epithelial cells of the proximal kidney.
Nanomedicine
; 22: 102108, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31655201
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 neighboring 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 reorganization. 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 remodeling. 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.
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Base de dados:
MEDLINE
Assunto principal:
Células Epiteliais
/
Receptores Purinérgicos P2X7
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Túbulos Renais Proximais
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article