RGD Reference Report - Periostin links mechanical strain to inflammation in abdominal aortic aneurysm. - Rat Genome Database

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Periostin links mechanical strain to inflammation in abdominal aortic aneurysm.

Authors: Yamashita, O  Yoshimura, K  Nagasawa, A  Ueda, K  Morikage, N  Ikeda, Y  Hamano, K 
Citation: Yamashita O, etal., PLoS One. 2013 Nov 19;8(11):e79753. doi: 10.1371/journal.pone.0079753. eCollection 2013.
RGD ID: 10041046
Pubmed: PMID:24260297   (View Abstract at PubMed)
PMCID: PMC3833967   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0079753   (Journal Full-text)

AIMS: Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, which contributes to the pathological remodeling of the extracellular matrix. Although mechanical stress has been suggested to promote inflammation in AAA, the molecular mechanism remains uncertain. Periostin is a matricellular protein known to respond to mechanical strain. The aim of this study was to elucidate the role of periostin in mechanotransduction in the pathogenesis of AAA. METHODS AND RESULTS: We found significant increases in periostin protein levels in the walls of human AAA specimens. Tissue localization of periostin was associated with inflammatory cell infiltration and destruction of elastic fibers. We examined whether mechanical strain could stimulate periostin expression in cultured rat vascular smooth muscle cells. Cells subjected to 20% uniaxial cyclic strains showed significant increases in periostin protein expression, focal adhesion kinase (FAK) activation, and secretions of monocyte chemoattractant protein-1 (MCP-1) and the active form of matrix metalloproteinase (MMP)-2. These changes were largely abolished by a periostin-neutralizing antibody and by the FAK inhibitor, PF573228. Interestingly, inhibition of either periostin or FAK caused suppression of the other, indicating a positive feedback loop. In human AAA tissues in ex vivo culture, MCP-1 secretion was dramatically suppressed by PF573228. Moreover, in vivo, periaortic application of recombinant periostin in mice led to FAK activation and MCP-1 upregulation in the aortic walls, which resulted in marked cellular infiltration. CONCLUSION: Our findings indicated that periostin plays an important role in mechanotransduction that maintains inflammation via FAK activation in AAA.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abdominal aortic aneurysm  ISOPostn (Mus musculus)10041046; 10041046protein:increased expression:aorta:RGD 
abdominal aortic aneurysm  IEP 10041046; 10041046protein:increased expression:aorta:RGD 
abdominal aortic aneurysm  ISOPOSTN (Homo sapiens)10041046; 10041046protein:increased expression:aorta:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of chemokine (C-X-C motif) ligand 2 production  IMP 10041046 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Postn  (periostin)

Genes (Mus musculus)
Postn  (periostin, osteoblast specific factor)

Genes (Homo sapiens)
POSTN  (periostin)


Additional Information