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Am J Physiol Heart Circ Physiol 289: H277-H284, 2005. First published March 18, 2005; doi:10.1152/ajpheart.01206.2004
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Activation of regenerating gene Reg in rat and human hearts in response to acute stress

Tatsuya Kiji,1 Yoshiko Dohi,2 Shin Takasawa,3 Hiroshi Okamoto,4 Akitaka Nonomura,5 and Shigeki Taniguchi1

Departments of 1Thoracic and Cardiovascular Surgery and 2Public Health, Nara Medical University School of Medicine, Kashihara, Nara; Departments of 3Biochemistry and 4Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai, Miyagi; and 5Department of Diagnostic Pathology, Nara Medical University School of Medicine, Nara, Japan

Submitted 1 December 2004 ; accepted in final form 10 March 2005

Recently, the regenerating gene (Reg) has been documented to play an important role in various regenerating tissues, but it is unknown whether the Reg gene could be activated in the heart. The aim of this study was to reveal the transcriptional activation of Reg in the heart in response to heart stress. We first found REG-1 protein expression in human hearts obtained from autopsied patients who died of myocardial infarction. REG protein was immunohistochemically stained in a fine granular pattern in the cytoplasm of cardiomyocytes. To demonstrate the activation profiles of Reg gene expression in the heart, we quantified the levels of Reg-1 mRNA in rat hearts after coronary artery ligation using real-time RT-PCR. Transient Reg-1 mRNA activation, peaking at 12 h after coronary ligation, was observed mainly in the atria, which was sevenfold higher compared with hearts with pressure overload due to aortic constriction. In contrast, Reg receptor mRNA was expressed intensely in damaged ventricles. Furthermore, Western blot analysis showed the corresponding pattern of Reg protein secretion into the serum after loading, and circulating levels of the protein after myocardial infarction were higher than those after aortic constriction. In conclusion, our results demonstrate for the first time the presence of the Reg/Reg receptor system in damaged hearts. In view of emerging evidence of Reg for tissue regeneration in a variety of tissues/organs, it is proposed that the damaged heart may be a target for Reg action and that Reg may protect against acute heart stress.

receptor; heart failure; myocardial infarction; pressure overload



Address for reprint requests and other correspondence: T. Kiji, Dept. of Thoracic and Cardiovascular Surgery, Nara Medical Univ. School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan (E-mail: t-kiji{at}naramed-u.ac.jp)




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