RGD Reference Report - Endothelial prostacyclin protects the kidney from ischemia-reperfusion injury. - Rat Genome Database

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Endothelial prostacyclin protects the kidney from ischemia-reperfusion injury.

Authors: Cao, Yingxue  Guan, Yi  Xu, Yun-Yu  Hao, Chuan-Ming 
Citation: Cao Y, etal., Pflugers Arch. 2019 Apr;471(4):543-555. doi: 10.1007/s00424-018-2229-6. Epub 2018 Nov 9.
RGD ID: 401959745
Pubmed: PMID:30413885   (View Abstract at PubMed)
PMCID: PMC6435627   (View Article at PubMed Central)
DOI: DOI:10.1007/s00424-018-2229-6   (Journal Full-text)

Prostacyclin, or PGI2, is a product of PGI synthase (PGIS), down-stream of cyclooxygenase pathway. PGI2 has been demonstrated to play an important role in maintaining renal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase are reported to increase the susceptibility of patients to acute kidney injury (AKI). This study explores the role of endothelium-derived prostacyclin in ischemia-reperfusion injury (I/RI). The renal PGIS expression and PGI2 production markedly increased following I/RI. Loss of one allele of PGIS gene or selective endothelial PGIS deletion (TEK-CRE PGISfl/fl mice) caused more severe renal damage following I/RI than control mice. Iloprost, a PGI2 analog, administered 30 min before the I/R surgery, markedly attenuated the renal damage in both control mice and TEK-CRE PGISfl/fl mice. Renal p-PKA expression significantly increased after I/RI in wild-type mice but not in the PGIS deletion mice, consistent with IP receptor mediating the protective effect. Further studies showed that PGIS deficiency was associated with reduced fluorescence microsphere accumulation in the kidney following I/R. Folic acid also induced marked kidney injury; however, endothelial PGIS deletion did not worsen kidney injury compared with wild-type mice. These studies indicate that PGIS-derived PGI2 can protect the kidney from acute injury caused by ischemia and reperfusion and PGIS/PGI2 is a potential intervention target for AKI.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanKidney Reperfusion Injury  ISOPtgis (Mus musculus)mRNA:increased expression:kidney (mouse)RGD 
PtgisRatKidney Reperfusion Injury  ISOPtgis (Mus musculus)mRNA:increased expression:kidney (mouse)RGD 
PtgisMouseKidney Reperfusion Injury  IEP mRNA:increased expression:kidney (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information