RGD Reference Report - Identification of potential therapeutic targets in hypertension-associated bladder dysfunction. - Rat Genome Database

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Identification of potential therapeutic targets in hypertension-associated bladder dysfunction.

Authors: Yono, M  Yoshida, M  Yamamoto, Y  Imanishi, A  Fukagawa, A  Latifpour, J  Eto, M 
Citation: Yono M, etal., BJU Int. 2010 Mar;105(6):877-83. doi: 10.1111/j.1464-410X.2009.08809.x. Epub 2009 Aug 18.
RGD ID: 9684972
Pubmed: PMID:19689474   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1464-410X.2009.08809.x   (Journal Full-text)

OBJECTIVE: To investigate differential gene expression profiles in the bladder of spontaneously hypertensive rat (SHR), as the underlying mechanisms involved in hypertension-associated bladder dysfunction remain to be clarified. MATERIALS AND METHODS: SHR and normotensive Wistar-Kyoto (WKY) rats were distributed initially in three groups: group 1 received doxazosin (30 mg/kg/day); group 2 received nifedipine (30 mg/kg/day); and group 3 received the vehicle orally for 4 weeks. The alterations in gene expression levels of candidate genes identified by microarray analysis with potential biological relevance were verified by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Voiding frequency was significantly higher, and mean voided volume was significantly lower in untreated SHRs than untreated WKY rats. Microarray analysis revealed that 25 of the differentially expressed genes in untreated SHRs compared to untreated WKY rats were related to G(s), G(i), G(q) and G(12/13) signalling, calcium handling, ion transport and smooth muscle-related genes. Furthermore, RT-PCR data, in accord with the microarray analysis, indicated that untreated SHRs had lower mRNA expression levels of Adcy2, Adcy3, Rgs2, Rgs3, Rgs4 and Arhgdia, and higher mRNA expression levels of Arhgef1, Arhgef11, Arhgef12, Geft, Rock1 and Rock2 than untreated WKY rats. The differential alterations in the micturition patterns and in the expression of several genes related to G-protein signalling pathway observed in SHRs were attenuated by treatment with doxazosin, but not nifedipine. CONCLUSION: Our data suggest that differential alterations in the expression of several genes related to G(s), G(q) and G(12/13) signalling pathways in the SHR bladder might be important in hypertension-associated bladder dysfunction.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RGS2Humanbladder disease treatmentISORgs2 (Rattus norvegicus)associated with hypertensionRGD 
RGS3Humanbladder disease treatmentISORgs3 (Rattus norvegicus)associated with hypertensionRGD 
RGS4Humanbladder disease treatmentISORgs4 (Rattus norvegicus)associated with hypertensionRGD 
Rgs2Ratbladder disease treatmentIEP associated with hypertensionRGD 
Rgs2Mousebladder disease treatmentISORgs2 (Rattus norvegicus)associated with hypertensionRGD 
Rgs3Ratbladder disease treatmentIEP associated with hypertensionRGD 
Rgs3Mousebladder disease treatmentISORgs3 (Rattus norvegicus)associated with hypertensionRGD 
Rgs4Ratbladder disease treatmentIEP associated with hypertensionRGD 
Rgs4Mousebladder disease treatmentISORgs4 (Rattus norvegicus)associated with hypertensionRGD 
ARHGDIAHumanhypertension  ISOArhgdia (Rattus norvegicus)mRNA:decreased expression:urinary bladderRGD 
ArhgdiaRathypertension  IEP mRNA:decreased expression:urinary bladderRGD 
ArhgdiaMousehypertension  ISOArhgdia (Rattus norvegicus)mRNA:decreased expression:urinary bladderRGD 

Objects Annotated

Genes (Rattus norvegicus)
Arhgdia  (Rho GDP dissociation inhibitor alpha)
Rgs2  (regulator of G-protein signaling 2)
Rgs3  (regulator of G-protein signaling 3)
Rgs4  (regulator of G-protein signaling 4)

Genes (Mus musculus)
Arhgdia  (Rho GDP dissociation inhibitor alpha)
Rgs2  (regulator of G-protein signaling 2)
Rgs3  (regulator of G-protein signaling 3)
Rgs4  (regulator of G-protein signaling 4)

Genes (Homo sapiens)
ARHGDIA  (Rho GDP dissociation inhibitor alpha)
RGS2  (regulator of G protein signaling 2)
RGS3  (regulator of G protein signaling 3)
RGS4  (regulator of G protein signaling 4)


Additional Information