title: Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes/Macrophages after Spinal Cord Injury.
abstract: Scar formation is a prominent pathological feature of traumatic central nervous system (CNS) injury, which has long been implicated as a major impediment to the CNS regeneration. However, the factors affecting such scar formation remain to be elucidated. We herein demonstrate that the extracellular matrix protein periostin (POSTN) is a key player in scar formation after traumatic spinal cord injury (SCI). Using high-throughput RNA sequencing data sets, we found that the genes involved in the extracellular region, such as POSTN, were significantly expressed in the injured spinal cord. The expression of POSTN peaked at 7 days after SCI, predominantly in the scar-forming pericytes. Notably, we found that genetic deletion of POSTN in mice reduced scar formation at the lesion site by suppressing the proliferation of the pericytes. Conversely, we found that recombinant POSTN promoted the migration capacity of the monocytes/macrophages and increased the expression of tumor necrosis factor-α from the monocytes/macrophages in vitro, which facilitated the proliferation of pericytes. Furthermore, we revealed that the pharmacological blockade of POSTN suppressed scar formation and improved the long-term functional outcome after SCI. Our findings suggest a potential mechanism whereby POSTN regulates the scar formation after SCI and provide significant evidence that POSTN is a promising therapeutic target for CNS injury.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yokota
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazu
authors.initials: K
authors.lastname: Kobayakawa
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kijima
authors.affiliation: Department of Transcriptomics, Japan Science and Technology Agency-Core Research for Evolutional Science and Technology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Department of Transcriptomics, Japan Science and Technology Agency-Core Research for Evolutional Science and Technology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harada
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ishihara
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: seokada@ortho.med.kyushu-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology*; D005260:Female; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D009416:Nerve Regeneration / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha