Anticubilin antisense RNA ameliorates adriamycin-induced tubulointerstitial injury in experimental rats

Am J Med Sci. 2011 Dec;342(6):494-502. doi: 10.1097/MAJ.0b013e31821952a2.


This study was designed to determine the effects of in vivo anticubilin antisense RNA on the uptake of albumin in tubules and on the tubulointerstitial injury in adriamycin-induced proteinuric rats. Adriamycin-treated rats were subjected to intrarenal delivery of adenoviral vectors encoding empty plasmid, cubilin sense RNA expression vector pAd-CUB or anticubilin antisense RNA expression vector pAd-ACUB on day 3. On days 14 and 28, half of the rats in each group were randomly selected to be killed, and blood samples, kidney tissues and 24-hour urine were collected. The diseased rats treated with pAdEasy-ACUB showed a 60% decrease in serum creatinine and glomerular filtration rate. Interestingly, the anticubilin antisense treatment led to a marked increase in albuminuria. Antisense treatment attenuated the histologic changes on both day 14 and day 28. The antisense treatment induced more than 60% recovery of adriamycin-induced injury, accompanied with 85% knockdown in the expression of cubilin protein and markedly decreased albumin deposition. Adriamycin induced an increase in the expression of monocyte chemoattractant protein-1, transforming growth factor-β and regulated on activation in normal T-cell expressed and secreted and the number of infiltrating cells, which was reversed by the antisense treatment. Anticubilin antisense RNA delivered by an adenoviral vector ameliorates albuminuria-induced glomerulosclerosis and tubulointerstitial damage in adriamycin nephrotic rats, indicating that cubilin could be a potential therapeutic target in proteinuric nephropathy.

MeSH terms

  • Adenoviridae
  • Albuminuria* / drug therapy
  • Animals
  • Blotting, Western
  • Chemokine CCL2 / metabolism
  • Creatinine / blood
  • Creatinine / urine
  • Doxorubicin / adverse effects*
  • Genetic Vectors
  • Glomerular Filtration Rate
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Male
  • Models, Animal
  • Proteinuria / drug therapy
  • RNA, Antisense / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / therapeutic use
  • Serum Albumin / metabolism
  • Transforming Growth Factor beta / metabolism


  • Chemokine CCL2
  • RNA, Antisense
  • Receptors, Cell Surface
  • Serum Albumin
  • Transforming Growth Factor beta
  • intrinsic factor-cobalamin receptor
  • Doxorubicin
  • Creatinine