LOX-1, an oxidized low-density lipoprotein receptor, was upregulated in the kidneys of chronic renal failure rats.
LOX-1 is a novel receptor for oxidized low-density lipoprotein (LDL) isolated from vascular endothelial cells and has been suggested to be involved in the formation of atherosclerotic and hypertensive vascular lesions. We previously reported that salt loading caused glomerulosclerosis and upregulation of LOX-1 in the kidney of Dahl salt-sensitive hypertensive rats. In the present study, we investigated LOX-1 expression in the remnant kidney, an established rat model for chronic renal failure. Six weeks after 5/6 nephrectomy, the rats showed elevated blood pressure, impaired renal function and increased renal expression of type I collagen. The LOX-1 gene expression in the remnant kidney was markedly increased compared with that in control rats, and immunohistochemical analysis showed that LOX-1 was widely expressed in the interstitial cells, whereas there was almost no staining in the glomeruli or tubules. Moreover, reduction of blood pressure by the angiotensin II type 1 (AT1) receptor antagonist candesartan significantly suppressed the renal LOX-1 expression, and this suppression was accompanied by amelioration of renal injury. These results suggest that enhanced renal expression of LOX-1 might play some roles in the progression of chronic renal failure in rats.
Ueno
Tomoko
T
Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan. nishinak-tky@umin.ac.jp
Kaname
Shinya
S
Takaichi
Kenmei
K
Nagase
Miki
M
Tojo
Akihiro
A
Onozato
Maristela Lika
ML
Fujita
Toshiro
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D024042:Collagen Type I / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D024042:Collagen Type I; C495136:OLR1 protein, rat; D044140:Receptor, Angiotensin, Type 1; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013777:Tetrazoles; C081643:candesartan