Increased osteopontin expression following renal ablation is attenuated by angiotensin type 1 receptor antagonism.
Osteopontin is an extracellular matrix protein that is upregulated in renal injury. The aim of this study was to explore the renal expression of osteopontin in a model of progressive renal injury following subtotal nephrectomy (STNx) in rats and the effects of angiotensin type1 (AT1) receptor antagonist irbesartan on osteopontin expression. STNx or a sham operation was performed in 8-week-old Sprague-Dawley rats. STNx rats were given either irbesartan (15 mg/g) or no treatment for 12 weeks. Upregulation of osteopontin mRNA expression was observed in injured renal tubules as assessed by in situ hybridization (42 +/- 8 dpm/mm(2) v.s. control 7.7 +/- 0.6 dpm/mm(2), p < 0.01). Increased osteopontin expression was closely related to infiltration of monocytes/macrophages and increased cellular proliferation. Double immunohistochemical staining demonstrated co-existence of proliferating cell nuclear antigen and osteopontin positive staining in individual cells in kidney sections from STNx rats. The increase in osteopontin expression was inhibited by the AT1 receptor antagonist irbesartan (6.9 +/- 1.2 dpm/mm(2)), associated with attenuation of impaired renal function and pathology as well as decreased monocyte/macrophage infiltration and cellular proliferation. These findings suggest that osteopontin is upregulated in STNx rats and is reduced by AT1 receptor antagonism.
Cao
Zemin
Z
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Center, Heidelberg West, Vic., Australia. cao@austin.unimelb.edu.au
Cox
Alison
A
Bonnet
Fabrice
F
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009392:Nephrectomy; D053495:Osteopontin; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013777:Tetrazoles / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D013777:Tetrazoles; D053495:Osteopontin; D000804:Angiotensin II; D000077405:Irbesartan