title: Differential expression of receptor tyrosine kinases and Shc in fetal and adult rat fibroblasts: toward defining scarless versus scarring fibroblast phenotypes.
abstract: The remarkable ability of the fetus to heal early gestation skin wounds without scarring remains poorly understood. Taking advantage of recent advances in signal transduction, the tyrosine phosphorylation patterns of fetal rat fibroblasts, representing the scarless cutaneous repair phenotype, and adult rat fibroblasts, representing scarforming phenotype, were examined whether there were inherent differences in cellular signaling. Specifically, correlation of the phosphorylation patterns with the expression levels of the signaling molecules that transmit information from the plasma membrane receptor to the nucleus was sought. By using three different cell lines of explanted fibroblasts from gestational day 13 fetal rat skin (n = 24) and 1-month-old postnatal adult rat skin (n = 3), immunoblotting was performed to compare tyrosine phosphorylation patterns. The results revealed five major protein bands of interest in fetal rat fibroblasts, but not in the adult rat fibroblasts. These phosphorylated protein bands are of interest because of their possible role in wound repair and may have the potential to regulate cellular responses to the extracellular matrix and their secondary signaling molecules. It was hypothesized that these bands represented receptor tyrosine kinases, epidermal growth factor receptor, and discoidin domain receptor 1, and their downstream adaptor protein Shc that binds receptor tyrosine kinases to transduce signals intracellularly. Furthermore, elevated expression of platelet-derived growth factor receptor-beta in adult compared with fetal fibroblasts was demonstrated, suggesting that decreased expression of certain growth factors may also be important for the scarless phenomenon to occur.
authors.affiliation: Department of Surgery, New York University Medical Center, NY 10016, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Chin
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
authors.forename: T Y
authors.initials: TY
authors.lastname: Lee
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: P B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Levinson
authors.forename: G K
authors.initials: GK
authors.lastname: Gittes
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism*; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D011506:Proteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism; D011975:Receptors, Mitogen / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014945:Wound Healing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D011506:Proteins; D011975:Receptors, Mitogen; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor