PMID- 22911870
OWN - NLM
STAT- MEDLINE
DCOM- 20130222
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse 
      model of scleroderma.
PG  - e41994
LID - 10.1371/journal.pone.0041994 [doi]
LID - e41994
AB  - OBJECTIVE: Periostin, a novel matricellular protein, is recently reported to play 
      a crucial role in tissue remodeling and is highly expressed under fibrotic 
      conditions. This study was undertaken to assess the role of periostin in 
      scleroderma. METHODS: Using skin from patients and healthy donors, the expression 
      of periostin was assessed by immunohistochemistry and immunoblotting analyses. 
      Furthermore, we investigated periostin(-/-) (PN(-/-)) and wild-type (WT) mice to 
      elucidate the role of periostin in scleroderma. To induce murine cutaneous 
      sclerosis, mice were subcutaneously injected with bleomycin, while untreated 
      control groups were injected with phosphate-buffered saline. Bleomycin-induced 
      fibrotic changes were compared in PN(-/-) and WT mice by histological analysis as 
      well as by measurements of profibrotic cytokine and extracellular matrix protein 
      expression levels in vivo and in vitro. To determine the downstream pathway 
      involved in periostin signaling, receptor neutralizing antibody and signal 
      transduction inhibitors were used in vitro. RESULTS: Elevated expression of 
      periostin was observed in the lesional skin of patients with scleroderma compared 
      with healthy donors. Although WT mice showed marked cutaneous sclerosis with 
      increased expression of periostin and increased numbers of myofibroblasts after 
      bleomycin treatment, PN(-/-) mice showed resistance to these changes. In vitro, 
      dermal fibroblasts from PN(-/-) mice showed reduced transcript expression of 
      alpha smooth actin and procollagen type-I alpha 1 (Col1alpha1) induced by 
      transforming growth factor beta 1 (TGFbeta1). Furthermore, recombinant mouse 
      periostin directly induced Col1alpha1 expression in vitro, and this effect was 
      inhibited by blocking the alphav integrin-mediated PI3K/Akt signaling either with 
      anti-alphav functional blocking antibody or with the PI3K/Akt kinase inhibitor 
      LY294002. CONCLUSION: Periostin plays an essential role in the pathogenesis of 
      Bleomycin-induced scleroderma in mice. Periostin may represent a potential 
      therapeutic target for human scleroderma.
FAU - Yang, Lingli
AU  - Yang L
AD  - Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
FAU - Serada, Satoshi
AU  - Serada S
FAU - Fujimoto, Minoru
AU  - Fujimoto M
FAU - Terao, Mika
AU  - Terao M
FAU - Kotobuki, Yorihisa
AU  - Kotobuki Y
FAU - Kitaba, Shun
AU  - Kitaba S
FAU - Matsui, Saki
AU  - Matsui S
FAU - Kudo, Akira
AU  - Kudo A
FAU - Naka, Tetsuji
AU  - Naka T
FAU - Murota, Hiroyuki
AU  - Murota H
FAU - Katayama, Ichiro
AU  - Katayama I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120724
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Col1a1 protein, mouse)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Integrin alphaV)
RN  - 0 (Postn protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11056-06-7 (Bleomycin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Bleomycin
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Collagen Type I/metabolism
MH  - Collagen Type I, alpha 1 Chain
MH  - Disease Models, Animal
MH  - Extracellular Matrix Proteins/metabolism
MH  - Female
MH  - Fibrosis
MH  - Gene Knockout Techniques
MH  - Humans
MH  - Integrin alphaV/metabolism
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Myofibroblasts/drug effects/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Scleroderma, Systemic/*enzymology/*pathology
MH  - Sclerosis
MH  - Skin/drug effects/*pathology
MH  - Transforming Growth Factor beta1/pharmacology
MH  - Up-Regulation/drug effects
MH  - Young Adult
PMC - PMC3404023
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/23 06:00
MHDA- 2013/02/23 06:00
PMCR- 2012/07/24
CRDT- 2012/08/23 06:00
PHST- 2012/03/16 00:00 [received]
PHST- 2012/06/28 00:00 [accepted]
PHST- 2012/08/23 06:00 [entrez]
PHST- 2012/08/23 06:00 [pubmed]
PHST- 2013/02/23 06:00 [medline]
PHST- 2012/07/24 00:00 [pmc-release]
AID - PONE-D-12-07736 [pii]
AID - 10.1371/journal.pone.0041994 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e41994. doi: 10.1371/journal.pone.0041994. Epub 2012 Jul 24.