Effects of Antisense Targeting to the Proximal Tubule

Noiri et al. used AS-ODN to inhibit production of inducible nitric oxide synthase (INOS) in an attempt to prevent NO production in an ischaemic kidney. A single intravenous injection of iNOS AS-ODN attenuated acute renal failure and reduced the morphological abnormalities [129], 

Oberbauer et al. reported inhibition of a sodium/phosphate (Na/Pi-2) co-transporter by phosphorothioated AS-ODN. A single intravenous injection of the AS-ODN inhibited both the mRNA and the protein for the Na/Pi-2 co-transporter, and conseqnently snppressed In-minal uptake of phosphate by the proximal tubules [130], 

Wang et al. injected a Texas-red-labelled phosphorothioated AS-ODN into the dopamine lA receptor in the rat renal interstitium. Fluorescence was detected after 24 h in both tubular epithelium and intra-renal vasculature. Treatment resulted in a 35% decrease in the dopamine lA receptor protein, causing a reduction in urinary sodium excretion and urine output [131], 

Rat kidneys were perfused ex situ with phosphorothioate intercellular adhesion molecule (ICAM)-l AS-ODN and exposed to 30 min cold or warm ischaemia. After this time the kidneys were transplanted to syngeneic nephrectomized rats. Treatment with 10 mg antisense reduced the harmful effect of transplantation on renal function [132] 

Cheng et al. showed that intravenous infusion of intracellular adhesion molecule (ICAM) AS-ODN markedly reduced ICAM-1 expression, alleviated infiltration of inflammatory cells and accumulation of extracellular matrix in the obstructed kidney of mice with unilateral obstruction of the ureter [133], 

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First, we will briefly review the different aspects that are of importance in the use of anti-sense for in vivo therapy. Second, we will describe the effects of antisense targeting to the proximal tubule of the kidney that have been obtained so far. 

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