RGD Reference Report - Basal expression of bone morphogenetic protein receptor is reduced in mild asthma. - Rat Genome Database

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Basal expression of bone morphogenetic protein receptor is reduced in mild asthma.

Authors: Kariyawasam, HH  Xanthou, G  Barkans, J  Aizen, M  Kay, AB  Robinson, DS 
Citation: Kariyawasam HH, etal., Am J Respir Crit Care Med. 2008 May 15;177(10):1074-81. Epub 2008 Feb 21.
RGD ID: 5129470
Pubmed: PMID:18292470   (View Abstract at PubMed)
DOI: DOI:10.1164/rccm.200709-1376OC   (Journal Full-text)

RATIONALE: Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway. OBJECTIVES: To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (ALK-2, ALK-3, ALK-6, and BMPRII) as well as evidence for activation of BMP signaling via detection of phosphorylated Smad1/5 (pSmad1/5) expression in asthmatic airways at baseline (compared with nonasthmatic controls), and after allergen challenge. METHODS: Bronchial biopsies were obtained from 6 nonasthmatic control volunteers, and 15 atopic patients with asthma (median age, 25 yr; median FEV(1)% predicted, 97%) at baseline, then at 24 hours and 7 days after allergen challenge. Expression of BMP ligands, receptors, and signaling was analyzed using immunohistochemistry. Measurements and Main Results: BMP ligand expression did not differ between asthmatic and control airways at baseline. Compared with the normal airway, there was significant down-regulation of ALK-2 (P = 0.001), ALK-6 (P = 0.0009), and BMPRII (P = 0.009) expression in asthma. Allergen challenge was associated with marked and sustained up-regulation of BMP-7 in airway epithelium (P = 0.017) and infiltrating inflammatory cells (P = 0.071) (predominantly in eosinophils, but also CD4(+) T cells, mast cells, and macrophages). Up-regulation of pSmad1/5 expression (P = 0.031), ALK-2 (P = 0.002), and ALK-6 (P < 0.001) was observed indicating active signaling. CONCLUSIONS: BMP receptor expression is down-regulated in the asthmatic airway, which may impede repair responses. Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signaling, and increases receptor expression, all of which may contribute to repair and control of inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IEP 5129470; 5129470protein:decreased expression:bronchusRGD 
asthma  ISOBMPR1B (Homo sapiens)5129470; 5129470protein:decreased expression:bronchusRGD 
asthma  ISOBMPR2 (Homo sapiens)5129470; 5129470protein:decreased expression:bronchusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmpr1b  (bone morphogenetic protein receptor type 1B)
Bmpr2  (bone morphogenetic protein receptor type 2)

Genes (Mus musculus)
Bmpr1b  (bone morphogenetic protein receptor, type 1B)
Bmpr2  (bone morphogenetic protein receptor type 2)

Genes (Homo sapiens)
BMPR1B  (bone morphogenetic protein receptor type 1B)
BMPR2  (bone morphogenetic protein receptor type 2)

Objects referenced in this article
Gene Bmpr1a bone morphogenetic protein receptor type 1A Rattus norvegicus

Additional Information