RGD Reference Report - Hypoxia and an angiogenic response in the partially obstructed rat bladder. - Rat Genome Database

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Hypoxia and an angiogenic response in the partially obstructed rat bladder.

Authors: Ghafar, MA  Anastasiadis, AG  Olsson, LE  Chichester, P  Kaplan, SA  Buttyan, R  Levin, RM 
Citation: Ghafar MA, etal., Lab Invest. 2002 Jul;82(7):903-9.
RGD ID: 9068887
Pubmed: PMID:12118092   (View Abstract at PubMed)

Previous molecular and blood flow studies performed on animal models of partial bladder outlet obstruction (PBOO) caused us to propose that bladder hypoxia/ischemia was a significant effector of the cellular and functional changes that occur in the bladder as a result of this condition. To confirm the occurrence of hypoxia in the partially obstructed bladder, we obtained rat bladders at increasing intervals following PBOO and measured biomarkers of hypoxia (intracellular formation of hypoxyprobe-1 adducts and expression of hypoxia inducible factor-1 alpha [HIF-1 alpha] protein) and whether such hypoxia might elicit an angiogenic response in the tissue. Rats receiving PBOO or controls were treated with hypoxyprobe-1 at increasing intervals subsequent to surgery and their bladders were sectioned and immunostained using an antibody that detects hypoxyprobe-1 adducts. Control rat bladders were unstained, whereas intense, but regionally restricted, hypoxyprobe-1 immunostaining was detected in all obstructed bladders in a unique pattern that changed over time. Proteins were extracted from bladders removed from similarly treated rats and were analyzed for the expression of the HIF-1 alpha protein as well as for expression of angiogenic regulatory factors (vascular endothelial growth factor, angiopoietin-1, and endostatin) using Western blotting techniques. HIF-1 alpha protein was not expressed in control bladders, however, the protein was highly up-regulated over the 2-week period after PBOO. Likewise, the expression of vascular endothelial growth factor (a downstream target of HIF-1 alpha action) and angiopoietin-1 was also up-regulated in obstructed bladders confirming an angiogenic response to this hypoxia. Enigmatically, however, expression of the antiangiogenic molecule endostatin was also up-regulated by chronic PBOO. These results further support the concept that hypoxia is involved in the cellular remodeling as well as in the progressive functional impairment exhibited by the urinary bladder after PBOO.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bladder neck obstruction  ISOHif1a (Rattus norvegicus)9068887; 9068887protein:increased expression:urinary bladder (rat)RGD 
bladder neck obstruction  IEP 9068887protein:increased expression:urinary bladder (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information