Activation of adenosine 2A receptors preserves structure and function of podocytes.
Adenosine 2A receptor (A(2A)R) activation was recently shown to be renoprotective in diabetic nephropathy. A(2A)R are found in glomeruli and have been shown to associate with the podocyte cytoskeletal protein alpha-actinin-4, but the effect of their activation on podocyte structure and function is unknown. Podocyte injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the selective A(2A)R agonist ATL313 was found to attenuate the resulting albuminuria and foot process fusion. The selective A(2A)R antagonist ZM241385 reversed the effects of ATL313. In vitro, A(2A)R mRNA and protein were expressed in a conditionally immortalized podocyte cell line, and A(2A)R-like immunoreactivity co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the increased podocyte permeability to albumin and disruption of the actin cytoskeleton that accompanied puromycin aminonucleoside-induced injury in vitro. ATL313 was ineffective, however, in the presence of the A(2A)R antagonist and in A(2A)R-deficient podocytes. It was concluded that A(2A)R activation reduces glomerular proteinuria, at least in part, by preserving the normal structure of podocyte foot processes, slit diaphragms, and actin cytoskeleton.
Awad
Alaa S
AS
Division of Nephrology, Box 133, University of Virginia Health System, Charlottesville, VA 22908, USA.
Rouse
Michael
M
Liu
Lixia
L
Vergis
Amy L
AL
Rosin
Diane L
DL
Linden
Joel
J
Sedor
John R
JR
Okusa
Mark D
MD
D058908:Adenosine A2 Receptor Agonists; D000419:Albuminuria / Q000517:prevention & control*; D000818:Animals; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000627:therapeutic use; D050199:Podocytes / Q000187:drug effects / Q000502:physiology*; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control; D011684:Purine Nucleosides / Q000009:adverse effects; D043683:Receptors, Adenosine A2 / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
C510376:ATL 313; D058908:Adenosine A2 Receptor Agonists; D010880:Piperidines; D011684:Purine Nucleosides; D043683:Receptors, Adenosine A2; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385