RGD Reference Report - Perturbations in Endothelial Dysfunction-Associated Pathways in the Nitrofen-Induced Congenital Diaphragmatic Hernia Model. - Rat Genome Database

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Perturbations in Endothelial Dysfunction-Associated Pathways in the Nitrofen-Induced Congenital Diaphragmatic Hernia Model.

Authors: Zhaorigetu, Siqin  Bair, Henry  Lu, Jonathan  Jin, Di  Olson, Scott D  Harting, Matthew T 
Citation: Zhaorigetu S, etal., J Vasc Res. 2017 Dec 8;55(1):26-34. doi: 10.1159/000484087.
RGD ID: 13504720
Pubmed: PMID:29216632   (View Abstract at PubMed)
DOI: DOI:10.1159/000484087   (Journal Full-text)

Although it is well known that nitrofen induces congenital diaphragmatic hernia (CDH), including CDH-associated lung hypoplasia and pulmonary hypertension (PH) in rodents, the mechanism of pathogenesis remains largely unclear. It has been reported that pulmonary artery (PA) endothelial cell (EC) dysfunction contributes to the development of PH in CDH. Thus, we hypothesized that there is significant alteration of endothelial dysfunction-associated proteins in nitrofen-induced CDH PAs. Pregnant SD rats received either nitrofen or olive oil on gestational day 9.5. The newborn rats were sacrificed and divided into a CDH (n = 81) and a control (n = 23) group. After PA isolation, the expression of PA endothelial dysfunction-associated proteins was assessed on Western blot and immunostaining. We demonstrate that the expression of C-reactive protein and endothelin-1 and its receptors, ETA and ETB, were significantly increased in the CDH PAs. Levels of phosphorylated myosin light chain were significantly elevated, but those of phosphorylated endothelial nitric oxide synthase, caveolin-1, and mechanistic target of rapamycin were significantly decreased in the CDH PAs. In this work, we elucidate alterations in the expression of endothelial dysfunction-associated proteins specific to nitrofen-induced CDH rodent PAs, thereby advancing our understanding of the critical role of endothelial dysfunction-associated pathways in the pathogenesis of nitrofen-induced CDH.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NOS3Humancongenital diaphragmatic hernia  ISONos3 (Rattus norvegicus)protein:decreased expression:pulmonary artery (rat)RGD 
Nos3Ratcongenital diaphragmatic hernia  IEP protein:decreased expression:pulmonary artery (rat)RGD 
Nos3Mousecongenital diaphragmatic hernia  ISONos3 (Rattus norvegicus)protein:decreased expression:pulmonary artery (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information