Role of central nervous system periostin in cerebral ischemia.
OBJECTIVE
Although periostin, an extracellular matrix glycoprotein, plays pivotal roles in survival, migration, and regeneration in various cells, its expression and function in the brain are still unknown. Here, we investigated the expression and role of periostin in the ischemic brain.


METHODS
Expression of full-length periostin (periostin 1 [Pn1]) and its splicing variant lacking exon 17 (periostin 2 [Pn2]) was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining in male C57BL6/J mice. The actions of periostin were examined in adult primary neuronal culture and in a transient middle cerebral artery occlusion (tMCAo) model.


RESULTS
Expression of Pn2, but not of Pn1, mRNA was markedly changed after tMCAo. Pn2 mRNA was decreased in the ischemic core at 3 hours after ischemia. At 24 hours, Pn2 mRNA was significantly increased in both the peri-ischemic and ischemic regions. Periostin was mainly observed in neurons in normal brain. However, neuronal expression of periostin was decreased temporarily in the ischemic region, but increased in astrocytes and around endothelial cells at 24 hours after tMCAo. Of importance, intracerebroventricular injection of Pn2 resulted in a significant reduction in infarct volume at 24 hours after tMCAo associated with phosphorylation of Akt. Also, the Pn2-treated mice survived longer until 1 week after tMCAo. Pn2 significantly inhibited neuronal death under hypoxia and stimulated neurite outgrowth.


CONCLUSIONS
Here, we demonstrated that periostin was expressed in the brain, and exogenous Pn2 exhibited neuroprotective effects and accelerated neurite outgrowth. Additional studies on periostin may provide new insights into the treatment of ischemic stroke.
Department of Clinical Gene Therapy, Osaka University, Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. morishit@cgt.med.osaka-u.ac.jp
Munehisa
M
Shimamura
Yoshiaki
Y
Taniyama
Naruto
N
Katsuragi
Nobutaka
N
Koibuchi
Mariko
M
Kyutoku
Naoyuki
N
Sato
Mohammad
M
Allahtavakoli
Kouji
K
Wakayama
Hironori
H
Nakagami
Ryuichi
R
Morishita
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000494:pharmacology*; D016923:Cell Death; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013997:Time Factors
D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C082838:Postn protein, mouse