Therapeutic angiogenesis in a murine model of limb ischemia by recombinant periostin and its fasciclin I domain.
Periostin, an extracellular matrix protein, is expressed in injured tissues, such as the heart with myocardial infarction, and promotes angiogenesis and tissue repair. However, the molecular mechanism associated with periostin-stimulated angiogenesis and tissue repair is still unclear. In order to clarify the role of periostin in neovascularization, we examined the effect of periostin in angiogenic potentials of human endothelial colony forming cells (ECFCs) in vitro and in an ischemic limb animal model. Recombinant periostin protein stimulated the migration and tube formation of ECFCs. To identify the functional domains of periostin implicated in angiogenesis, five fragments of periostin, including four repeating FAS-1 domains and a carboxyl terminal domain, were expressed in Escherichia coli and purified to homogeneity. Of the five different domains, the first FAS-1 domain stimulated the migration and tube formation of human ECFCs as potent as the whole periostin. Chemotactic migration of ECFCs induced by the full length and the first FAS-1 domain of periostin was abrogated by blocking antibodies against β3 and β5 integrins. Intramuscular injection of the full length and the first FAS-1 domain of periostin into the ischemic hindlimb of mice attenuated severe limb loss and promoted blood perfusion and homing of intravenously administered ECFCs to the ischemic limb. These results suggest that the first FAS-1 domain is responsible for periostin-induced migration and angiogenesis and it can be used as a therapeutic tool for treatment of peripheral artery occlusive disease by stimulating homing of ECFCs.
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Ba Reun
BR
Kim
Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Il Ho
IH
Jang
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Sang Hun
SH
Shin
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Yang Woo
YW
Kwon
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Soon Chul
SC
Heo
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Eun-Jung
EJ
Choi
Department of Orthopaedic Surgery, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Jung Sub
JS
Lee
Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea; Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Gyeongsangnam-do, Republic of Korea. Electronic address: jhkimst@pusan.ac.kr.
Jae Ho
JH
Kim
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C512835:POSTN protein, human; D011994:Recombinant Proteins; C051641:fasciclin I
Endothelial colony forming cell; Homing; Ischemia; Neovascularization; Periostin