title: Anticubilin antisense RNA ameliorates adriamycin-induced tubulointerstitial injury in experimental rats.
abstract: 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.
authors: Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing, China.
authors: Jun
authors: J
authors: Liu
authors: Kailong
authors: K
authors: Li
authors: Yani
authors: Y
authors: He
authors: Jianguo
authors: J
authors: Zhang
authors: Huiming
authors: H
authors: Wang
authors: Jurong
authors: J
authors: Yang
authors: Jun
authors: J
authors: Zhan
authors: Haijun
authors: H
authors: Liang
mesh_terms: D000256:Adenoviridae; D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D004317:Doxorubicin / Q000009:adverse effects*; D005822:Genetic Vectors; D005919:Glomerular Filtration Rate; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D011507:Proteinuria / Q000188:drug therapy; D016372:RNA, Antisense / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; C029486:intrinsic factor-cobalamin receptor; D004317:Doxorubicin; D003404:Creatinine