Periostin is essential for cardiac healing after acute myocardial infarction.
Acute myocardial infarction (AMI) is a common and lethal heart disease, and the recruitment of fibroblastic cells to the infarct region is essential for the cardiac healing process. Although stiffness of the extracellular matrix in the infarct myocardium is associated with cardiac healing, the molecular mechanism of cardiac healing is not fully understood. We show that periostin, which is a matricellular protein, is important for the cardiac healing process after AMI. The expression of periostin protein was abundant in the infarct border of human and mouse hearts with AMI. We generated periostin(-/-) mice and found no morphologically abnormal cardiomyocyte phenotypes; however, after AMI, cardiac healing was impaired in these mice, resulting in cardiac rupture as a consequence of reduced myocardial stiffness caused by a reduced number of alpha smooth muscle actin-positive cells, impaired collagen fibril formation, and decreased phosphorylation of FAK. These phenotypes were rescued by gene transfer of a spliced form of periostin. Moreover, the inhibition of FAK or alphav-integrin, which blocked the periostin-promoted cell migration, revealed that alphav-integrin, FAK, and Akt are involved in periostin signaling. Our novel findings show the effects of periostin on recruitment of activated fibroblasts through FAK-integrin signaling and on their collagen fibril formation specific to healing after AMI.
Shimazaki
Masashi
M
Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Nakamura
Kazuto
K
Kii
Isao
I
Kashima
Takeshi
T
Amizuka
Norio
N
Li
Minqi
M
Saito
Mitsuru
M
Fukuda
Keiichi
K
Nishiyama
Takashi
T
Kitajima
Satoshi
S
Saga
Yumiko
Y
Fukayama
Masashi
M
Sata
Masataka
M
Kudo
Akira
A
D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002921:Cicatrix / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse