title: Keratin gene expression profiles after digit amputation in C57BL/6 vs. regenerative MRL mice imply an early regenerative keratinocyte activated-like state.
abstract: Mouse strains C57BL/6 (B6) and MRL were studied by whole mouse genome chip microarray analyses of RNA isolated from amputation sites at different times pre- and postamputation at the midsecond phalange of the middle digit. Many keratin genes were highly differentially expressed. All keratin genes were placed into three temporal response classes determined by injury/preinjury ratios. One class, containing only Krt6 and Krt16, were uniquely expressed relative to the other two classes and exhibited different temporal responses in MRL vs. B6. Immunohistochemical staining for Krt6 and Krt16 in tissue sections, including normal digit, flank skin, and small intestine, and from normal and injured ear pinna tissue exhibited staining differences in B6 (low) and MRL (high) that were consistent with the microarray results. Krt10 staining showed no injury-induced differences, consistent with microarray expression. We analyzed Krt6 and Krt16 gene association networks and observed in uninjured tissue several genes with higher expression levels in MRL, but not B6, that were associated with the keratinocyte activated state: Krt6, Krt16, S100a8, S100a9, and Il1b; these data suggest that keratinocytes in the MRL strain, but not in B6, are in an activated state prior to wounding. These expression levels decreased in MRL at all times postwounding but rose in the B6, peaking at day 3. Other keratins significantly expressed in the normal basal keratinocyte state showed no significant strain differences. These data suggest that normal MRL skin is in a keratinocyte activated state, which may provide it with superior responses to wounding.
authors.affiliation: Center for Intelligent Biomaterials, Department of Chemistry, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Leferovich
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Zhang
authors.forename: Khamilia
authors.initials: K
authors.lastname: Bedelbaeva
authors.forename: Dmitri
authors.initials: D
authors.lastname: Gourevitch
authors.forename: Cathy J
authors.initials: CJ
authors.lastname: Hatcher
authors.forename: Craig T
authors.initials: CT
authors.lastname: Basson
authors.forename: Ellen
authors.initials: E
authors.lastname: Heber-Katz
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Marx
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D005260:Female; D056426:Genetic Loci; D016678:Genome; D006614:Hindlimb / Q000601:surgery*; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D007633:Keratins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration / Q000235:genetics / Q000528:radiation effects*; D059467:Transcriptome; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: D007633:Keratins
keywords: MRL mouse; digit amputation; keratin genes; keratinocyte activation cycle; microarrays