A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration.
Unlike in mammals, fish retinal ganglion cells (RGCs) have a capacity to repair their axons even after optic nerve transection. In our previous study, we isolated a tissue type transglutaminase (TG) from axotomized goldfish retina. The levels of retinal TG (TG(R)) mRNA increased in RGCs 1-6weeks after nerve injury to promote optic nerve regeneration both in vitro and in vivo. In the present study, we screened other types of TG using specific FITC-labeled substrate peptides to elucidate the implications for optic nerve regeneration. This screening showed that the activity of only cellular coagulation factor XIII (cFXIII) was increased in goldfish optic nerves just after nerve injury. We therefore cloned a full-length cDNA clone of FXIII A subunit (FXIII-A) and studied temporal changes of FXIII-A expression in goldfish optic nerve and retina during regeneration. FXIII-A mRNA was initially detected at the crush site of the optic nerve 1h after injury; it was further observed in the optic nerve and achieved sustained long-term expression (1-40days after nerve injury). The cells producing FXIII-A were astrocytes/microglial cells in the optic nerve. By contrast, the expression of FXIII-A mRNA and protein was upregulated in RGCs for a shorter time (3-10days after nerve injury). Overexpression of FXIII-A in RGCs achieved by lipofection induced significant neurite outgrowth from unprimed retina, but not from primed retina with pretreatment of nerve injury. Addition of extracts of optic nerves with injury induced significant neurite outgrowth from primed retina, but not from unprimed retina without pretreatment of nerve injury. The transient increase of cFXIII in RGCs promotes neurite sprouting from injured RGCs, whereas the sustained increase of cFXIII in optic nerves facilitates neurite elongation from regrowing axons.
Division of Health Sciences, Graduate School of Medicine, Kanazawa University, Kanazawa 920-0942, Japan. sugitani@staff.kanazawa-u.ac.jp
Kayo
K
Sugitani
Kazuhiro
K
Ogai
Kiyotaka
K
Hitomi
Kayo
K
Nakamura-Yonehara
Takafumi
T
Shintani
Masaharu
M
Noda
Yoshiki
Y
Koriyama
Hideji
H
Tanii
Toru
T
Matsukawa
Satoru
S
Kato
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005176:Factor XIII / Q000737:chemistry / Q000378:metabolism*; D006054:Goldfish; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009416:Nerve Regeneration; D009900:Optic Nerve / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000201:enzymology / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D012333:RNA, Messenger; D005176:Factor XIII; D011503:Transglutaminases