title: Collagen loss and impaired wound healing is associated with c-Myb deficiency.
abstract: Collagen type I serves as an abundant structural and signalling component of skin. It is also an established target gene of the transcription factor, c-Myb. When c-myb-/- embryos were examined it was observed that their skin was markedly thinner than normal. Importantly, immunohistochemical investigation showed complete absence of collagen type I. Although these homozygous knock-out embryos fail to develop beyond day 15, fibroblasts established from these embryos (mouse embryonic fibroblasts [MEFs]) show defective proliferative responses. Furthermore, in vitro scratch wound assays demonstrated that these c-myb-/- MEFs also exhibit slower closure than their wild-type counterparts. Embryonic lethality has meant that examination of the role of c-Myb in adult mouse skin has not been reported to date. However, in view of the abundance of collagen type I in normal skin, its role in skin integrity and the in vitro data showing proliferative and migration defects in c-myb-/- MEFs, we investigated the consequences of heterozygous c-myb loss in adult mice on the complex process of skin repair in response to injury. Our studies clearly demonstrate that heterozygous c-myb deficiency has a functional effect on wound repair, collagen type I levels and, in response to wounding, transforming growth factor-beta1 (an important collagen stimulating factor) induction expression is aberrantly high. Manipulation of c-Myb may therefore provide new therapeutic opportunities for improving wound repair while uncontrolled expression may underpin some fibrotic disorders.
authors.affiliation: Child Health Research Institute, North Adelaide, South Australia and School of Pharmacy and Medical Sciences, University of South Australia, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Kopecki
authors.forename: M M
authors.initials: MM
authors.lastname: Luchetti
authors.forename: D H
authors.initials: DH
authors.lastname: Adams
authors.forename: X
authors.initials: X
authors.lastname: Strudwick
authors.forename: T
authors.initials: T
authors.lastname: Mantamadiotis
authors.forename: A
authors.initials: A
authors.lastname: Stoppacciaro
authors.forename: A
authors.initials: A
authors.lastname: Gabrielli
authors.forename: R G
authors.initials: RG
authors.lastname: Ramsay
authors.forename: A J
authors.initials: AJ
authors.lastname: Cowin
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020570:Genes, myb; D006579:Heterozygote; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D020598:Proto-Oncogene Proteins c-myb / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D017931:DNA Primers; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta