title: Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.
abstract: Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and TNF-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-α production model using spleen cells revealed that TNF-α production was significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in kl/kl mouse may have a role to increase TNF-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: mau5187@yahoo.co.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: hirohash@sapmed.a.cjp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Musashi
authors.initials: M
authors.lastname: Kayama
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Yotsuyanagi
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012867:Skin / Q000293:injuries* / Q000503:physiopathology*; D013045:Species Specificity; D016896:Treatment Outcome; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: FGF23; Klotho; TNF-α; Wound healing