RGD Reference Report - Natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system has inhibitory effects in renal fibrosis in mice. - Rat Genome Database

Send us a Message



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

Natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system has inhibitory effects in renal fibrosis in mice.

Authors: Nishikimi, T  Inaba-Iemura, C  Ishimura, K  Tadokoro, K  Koshikawa, S  Ishikawa, K  Akimoto, K  Hattori, Y  Kasai, K  Minamino, N  Maeda, N  Matsuoka, H 
Citation: Nishikimi T, etal., Regul Pept. 2009 Apr 10;154(1-3):44-53. doi: 10.1016/j.regpep.2009.02.006. Epub 2009 Feb 15.
RGD ID: 7247722
Pubmed: PMID:19223006   (View Abstract at PubMed)
DOI: DOI:10.1016/j.regpep.2009.02.006   (Journal Full-text)

OBJECT: This study was designed to examine whether natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system attenuates renal fibrosis in a unilateral ureteral obstruction (UUO) model and also examined the mechanism involved. METHODS: Three groups were studied: untreated UUO in wild-type mice; untreated UUO in NPR-A KO mice; and ANP treated (0.05 microg/kg/min) UUO in wild-type mice. We measured histological and immunohistochemical findings (alpha-SMA and F4/80), tissue cGMP levels, various mRNA expression levels by real-time PCR analysis, and transcription factor levels (AP-1 and NF-kappaB) in renal tissue. RESULTS: Compared with wild-type UUO mice, NPRA-KO UUO mice had abnormal morphological findings (fibrous area: +26%, alpha-SMA expression: +30%) with lower tissue cGMP levels and increases in the mRNA expression levels of TGF-beta, collagen I, collagen III, PAI-1, renin and angiotensinogen, whereas there were no differences in F4/80 positive cells or the mRNA expression levels of ICAM-1, osteopontin, or MCP-1 between the two groups. In contrast, ANP pre-treatment significantly improved morphological changes with increase of tissue cGMP levels and reduction in the mRNA expression level of TGF-beta, collagen I, collagen III, PAI-1, ICAM-1, osteopontin, MCP-1, renin, and angiotensinogen. NPRA-KO UUO mice had higher AP-1 levels than wild-type UUO mice and ANP pre-treatment reduced AP-1 and NF-kappaB activity. CONCLUSION: The endogenous natriuretic peptide/NPR-A system may inhibit renal fibrosis partly via inhibition of the angiotensin/AP-1/TGF-beta/collagen pathway and exogenous ANP pre-treatment may inhibit it partly via both the angiotensin/AP-1/TGF-beta/collagen and NF-kappaB/inflammatory pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Nppa  (natriuretic peptide A)
Npr1  (natriuretic peptide receptor 1)

Genes (Mus musculus)
Nppa  (natriuretic peptide type A)
Npr1  (natriuretic peptide receptor 1)

Genes (Homo sapiens)
NPPA  (natriuretic peptide A)
NPR1  (natriuretic peptide receptor 1)

Objects referenced in this article
Gene PLIN2 perilipin 2 Homo sapiens

Additional Information