Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals.
BACKGROUND
Subepithelial fibrosis is a cardinal feature of bronchial asthma. Collagen I, III, and V; fibronectin; and tenascin-C are deposited in the lamina reticularis. Extensive evidence supports the pivotal role of IL-4 and IL-13 in subepithelial fibrosis; however, the precise mechanism remains unclear. We have previously identified the POSTN gene encoding periostin as an IL-4/IL-13-inducible gene in bronchial epithelial cells. Periostin is thought to be an adhesion molecule because it possesses 4 fasciclin I domains.


OBJECTIVE
We explore the possibility that periostin is involved in subepithelial fibrosis in bronchial asthma.


METHODS
We analyzed induction of periostin in lung fibroblasts by IL-4 or IL-13. We next analyzed expression of periostin in patients with asthma and in ovalbumin-sensitized and ovalbumin-inhaled mice. Furthermore, we examined the binding ability of periostin to other extracellular matrix proteins.


RESULTS
Both IL-4 and IL-13 induced secretion of periostin in lung fibroblasts independently of TGF-beta. Periostin colocalized with other extracellular matrix proteins involved in subepithelial fibrosis in both asthma patients and ovalbumin-sensitized and ovalbumin-inhaled wild-type mice, but not in either IL-4 or IL-13 knockout mice. Periostin had an ability to bind to fibronectin, tenascin-C, collagen V, and periostin itself.


CONCLUSIONS
Periostin secreted by lung fibroblasts in response to IL-4 and/or IL-13 is a novel component of subepithelial fibrosis in bronchial asthma. Periostin may contribute to this process by binding to other extracellular matrix proteins.


CONCLUSIONS
Periostin induced by IL-4/IL-13 shows promise in inhibiting subepithelial fibrosis in bronchial asthma.
Takayama
Go
G
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Arima
Kazuhiko
K
Kanaji
Taisuke
T
Toda
Shuji
S
Tanaka
Hiroyuki
H
Shoji
Shunsuke
S
McKenzie
Andrew N J
AN
Nagai
Hiroichi
H
Hotokebuchi
Takao
T
Izuhara
Kenji
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D004848:Epithelium / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D018793:Interleukin-13; C512835:POSTN protein, human; C082838:Postn protein, mouse; D012333:RNA, Messenger; D015847:Interleukin-4; D010047:Ovalbumin