RGD Reference Report - Differential regulation of osteopontin expression in the clipped and nonclipped kidney of two-kidney, one-clip hypertensive rats. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Differential regulation of osteopontin expression in the clipped and nonclipped kidney of two-kidney, one-clip hypertensive rats.

Authors: Gauer, S  Hartner, A  Hauser, IA  Fierlbeck, W  Eberhardt, W  Geiger, H 
Citation: Gauer S, etal., Am J Hypertens. 2003 Mar;16(3):214-22.
RGD ID: 1581326
Pubmed: PMID:12620700   (View Abstract at PubMed)

BACKGROUND: Osteopontin (Opn) is highly upregulated in many different animal models of renal disease, where it is suspected to participate in progression of the disease. In some models, angiotensin II (Ang II) seems to induce the elevated Opn production. Therefore, we examined the regulation of Opn in two-kidney, one-clip (2K1C) hypertensive rats, in which Ang II mediates the elevated blood pressure. METHODS: At days 7, 14, and 28, the clipped and nonclipped kidneys of hypertensive or sham-operated rats were analyzed for osteopontin protein, mRNA expression and mononuclear cell infiltration by imumunohistochemistry, in situ hybridization, and Northern blot analysis. Rats were treated with the Ang II type 1 receptor antagonist Valsartan starting 14 days after clipping. RESULTS: In sham-operated rats, Opn was mainly localized to cells of the thin ascending limbs of the outer medulla. No significant Opn staining was observed in cortical tubules. Focally defined tubular cortical Opn staining was observed in clipped and contralateral kidneys of hypertensive animals at days 14 and 28. Osteopontin protein expression correlated with the mRNA expression detected by in situ hybridization and Northern blot. Treatment with Valsartan reduced osteopontin staining by 51%, mRNA by 47%, and mononuclear cell number by 97% in nonclipped kidneys compared to untreated two-kidney, one-clip animals. In clipped kidneys, however, Opn protein and mRNA expression was not reduced, but a 240% increase in interstitial mononuclear cell number was observed. CONCLUSIONS: Osteopontin is involved in the induction of nephrosclerosis in renovascular hypertension, probably by a mechanism augmenting monocyte infiltration. Angiotensin II appears to be an important inducer of Opn in the nonclipped kidney. Ischemic conditions may regulate Opn expression in the clipped kidney.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renovascular hypertension  ISOSpp1 (Rattus norvegicus)1581326; 1581326 RGD 
renovascular hypertension  IDA 1581326 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Spp1  (secreted phosphoprotein 1)

Genes (Mus musculus)
Spp1  (secreted phosphoprotein 1)

Genes (Homo sapiens)
SPP1  (secreted phosphoprotein 1)


Additional Information