RGD Reference Report - Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: to establish a suitable model for study of airway mucus hypersecretion in chronic obstructive pulmonary disease. - Rat Genome Database

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Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: to establish a suitable model for study of airway mucus hypersecretion in chronic obstructive pulmonary disease.

Authors: Nie, YC  Wu, H  Li, PB  Luo, YL  Zhang, CC  Shen, JG  Su, WW 
Citation: Nie YC, etal., Pulm Pharmacol Ther. 2012 Oct;25(5):349-56. doi: 10.1016/j.pupt.2012.06.004. Epub 2012 Jun 23.
RGD ID: 7204496
Pubmed: PMID:22732689   (View Abstract at PubMed)
DOI: DOI:10.1016/j.pupt.2012.06.004   (Journal Full-text)

There is a need of in vivo COPD models for mucus hypersecretion study. The current study compared three rat models induced by cigarette smoke (CS) exposure alone or combined with pre- or post-treatment with lipopolysaccharide (LPS). Forty rats were randomly divided into the four following groups: control group, LPS + CS group (CS exposure for 4-wk combined with LPS pretreatment), CS group (CS exposure for 6-wk), CS + LPS group (CS exposure for 6-wk combined with LPS post-treatment). The results showed that both CS and CS + LPS groups had more severe pro-inflammatory cytokines secretion, inflammatory cells infiltration, and emphysema as compared to that in LPS + CS group animals. From the PAS staining sections, we found a remarkable hyperplasia of goblet-cell in epitheliums of trachea, bronchi, and bronchiole of all of three modeling groups, especially in CS and CS + LPS groups. From the western-blotting results, there were significant increase in the activities of NF-kappaB, AP-1, EGFR, TLR4, and MAPKs in all of three modeling groups, while HDAC2 activity was remarkably repressed in CS group only. Moreover, the expression and secretion of MUC5AC were exhibited significant increase in all of three modeling groups, which correlated well with the total transcription activity integration of NF-kappaB, AP-1, and HDAC2 (r = 0.946, p < 0.01). These results indicated that MUC5AC hypersecretion is consistent with activation of EGFR-AP-1/NF-kappaB and TLR4-AP-1/NF-kappaB signaling pathways, as well as repression of HDAC2 activity. Based on these results, we speculated that the 6-wk CS exposure rat model is a reliable COPD rat model, while the 6-wk CS exposure combined with LPS post-treatment rat model is a suitable COPD exacerbation model for mucus hypersecretion study.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chronic obstructive pulmonary disease  ISOEgfr (Rattus norvegicus)7204496; 7204496 RGD 
chronic obstructive pulmonary disease  IEP 7204496 RGD 
chronic obstructive pulmonary disease  ISOHdac2 (Rattus norvegicus)7204496; 7204496protein:decreased expression:lung:RGD 
chronic obstructive pulmonary disease  IEP 7204496protein:decreased expression:lung:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Hdac2  (histone deacetylase 2)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)
Hdac2  (histone deacetylase 2)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)
HDAC2  (histone deacetylase 2)


Additional Information