Periostin is essential for cardiac healing after acute myocardial infarction

Masashi Shimazaki, Kazuto Nakamura, Isao Kii, Takeshi Kashima, Norio Amizuka, Minqi Li, Mitsuru Saito, Keiichi Fukuda, Takashi Nishiyama, Satoshi Kitajima, Yumiko Saga, Masashi Fukayama, Masataka Sata, Akira Kudo

Research output: Contribution to journalArticle

296 Citations (Scopus)

Abstract

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 α 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 αv-integrin, which blocked the periostin-promoted cell migration, revealed that αv-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. JEM

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalJournal of Experimental Medicine
Volume205
Issue number2
DOIs
Publication statusPublished - 2008 Feb 18

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Shimazaki, M., Nakamura, K., Kii, I., Kashima, T., Amizuka, N., Li, M., Saito, M., Fukuda, K., Nishiyama, T., Kitajima, S., Saga, Y., Fukayama, M., Sata, M., & Kudo, A. (2008). Periostin is essential for cardiac healing after acute myocardial infarction. Journal of Experimental Medicine, 205(2), 295-303. https://doi.org/10.1084/jem.20071297