title: Phenotypic and functional modulation of 20-30 year old dermal fibroblasts by mid- and late-gestational keratinocytes in vitro.
abstract: Fetal wound healing occurs rapidly and without scar formation early in gestation, but the mechanisms underlying this scarless healing are poorly understood. This study explores the phenotypic and functional modulation of 20-30 year old dermal fibroblasts by mid- and late-gestational keratinocytes (KCs) in vitro. Human KCs of different gestational ages were isolated, characterized, and co-cultured with human 20-30 year old fibroblasts. Gene expression and protein levels of TGF-β family members, precollagen, collagen, matrix metalloproteinases (MMPs), and the tissue inhibitors of metalloproteinases (TIMPs) were measured in the fibroblasts. Mid-gestational KCs promoted faster proliferation and migration of fibroblasts than late-gestational KCs. Additionally, significant differences in gene expression and protein levels of some markers were observed in fibroblasts co-cultured with mid- or late-gestational KCs. Fibroblasts co-cultured with mid-gestational KCs for 48 h exhibited downregulated gene expression of precollagen 1, collagen 1, TGF-β1, TGF-β2, TIMP-2 and TIMP-3, while precollagen 3, collagen 3, TGF-β3, and MMP-1, -2, -3, -9 and -14 were upregulated. In contrast, late-gestational KCs exhibited downregulated TIMP-1, TIMP-2 and TIMP-3 levels, while collagen 1, TGF-β2, TGF-β3, and MMP-2, -3, -9 and -14 were upregulated. Moreover, statistically significant differences in expression levels of precollagen 1, precollagen 3, collagen 1, TGF-β1, -β2, and -β3, MMP-1, -3 and MMP-14, TIMP-1 and TIMP-2 were found between fibroblasts co-cultured with mid- and late-gestational KCs. Furthermore, cytokine levels of IL-1a and HB-EGF were found to be statistically different between conditioned medium from mid- and late-gestational KCs. Therefore, the gestational age of KCs appears to have an important effect on scarless wound healing in the human fetus.
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China; Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Dianbao
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of General Practice, The First Affiliated Hospital of China Medical, Shenyang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China. Electronic address: pangxining@126.com.
authors.forename: Xining
authors.initials: X
authors.lastname: Pang
mesh_terms: D000328:Adult; D002921:Cicatrix / Q000235:genetics*; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D020405:Dermis / Q000166:cytology*; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053582:Interleukin-1alpha / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics; D010641:Phenotype; D011347:Procollagen / Q000235:genetics; D012867:Skin / Q000166:cytology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics*; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D066257:Heparin-binding EGF-like Growth Factor; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D011347:Procollagen; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D053505:Matrix Metalloproteinases, Secreted
keywords: Cytokines; Fetus; Fibroblasts; Keratinocytes; Scarless; Wound healing