RGD Reference Report - Intratracheal administration of p38alpha short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats. - Rat Genome Database

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Intratracheal administration of p38alpha short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats.

Authors: Lv, X  Tan, J  Liu, D  Wu, P  Cui, X 
Citation: Lv X, etal., J Heart Lung Transplant. 2012 Jun;31(6):655-62. doi: 10.1016/j.healun.2012.03.001. Epub 2012 Apr 13.
RGD ID: 7240537
Pubmed: PMID:22503847   (View Abstract at PubMed)
DOI: DOI:10.1016/j.healun.2012.03.001   (Journal Full-text)

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) remains a significant problem after lung transplantation. A crucial signaling enzyme involved in inflammation and apoptosis during LIRI is p38 mitogen-activated protein kinase (MAPK). Gene silencing of p38alpha by short hairpin RNA (shRNA) can downregulate p38alpha expression. The lungs have an extremely large surface area, which makes the absorption of shRNA highly effective. Therefore, we evaluated the therapeutic efficacy of p38alpha shRNA plasmids in a rat model of lung transplantation. METHODS: The delivery of p38alpha shRNA plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. Control animals received scrambled shRNA plasmids. Reverse-transcription polymerase chain reaction and Western blots were used to assess gene silencing efficacy. The therapeutic effects of shRNA plasmids were evaluated by lung function tests. We determined the levels of inflammatory cytokines, the level of intercellular adhesion molecule 1 (ICAM-1), c-Myc mRNA expression, and ICAM-1 protein expression, and the presence of cell apoptosis. RESULTS: Rats administered p38alpha shRNA plasmids showed a significant downregulation in lung expression of p38alpha transcripts and protein levels. Compared with the control group, the p38alpha shRNA group showed a higher pulmonary vein oxygen level, lower wet weight-to-dry weight ratio, lower lung injury score, and lower serum levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-8. Messenger RNA levels of ICAM-1 and c-Myc in the p38alpha shRNA group were dramatically lower than in the control group. Levels of ICAM-1 protein expression exhibited a similar trend. Cell apoptosis decreased in the p38alpha shRNA group vs the control group. CONCLUSION: Intratracheal administration of p38alpha shRNA plasmids provided therapeutic effects in a rat model of lung transplantation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Lung Reperfusion Injury treatmentISOIcam1 (Rattus norvegicus)7240537; 7240537 RGD 
Lung Reperfusion Injury treatmentIEP 7240537; 7240537 RGD 
Lung Reperfusion Injury treatmentISOMyc (Rattus norvegicus)7240537; 7240537 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Icam1  (intercellular adhesion molecule 1)
Myc  (MYC proto-oncogene, bHLH transcription factor)

Genes (Mus musculus)
Icam1  (intercellular adhesion molecule 1)
Myc  (myelocytomatosis oncogene)

Genes (Homo sapiens)
ICAM1  (intercellular adhesion molecule 1)
MYC  (MYC proto-oncogene, bHLH transcription factor)


Additional Information