Phenotypic and functional modulation of 20-30 year old dermal fibroblasts by mid- and late-gestational keratinocytes in vitro

被引:10
作者
Wang, Zhe [1 ,2 ,3 ]
Liu, Xiaoyu [1 ,2 ]
Zhang, Dianbao [1 ,2 ]
Wang, Xiliang [1 ,2 ]
Zhao, Feng [1 ,2 ]
Zhang, Tao [1 ,2 ]
Wang, Rui [1 ,2 ]
Lin, Xuewen [1 ,2 ]
Shi, Ping [4 ]
Pang, Xining [1 ,2 ]
机构
[1] China Med Univ, Dept Stem Cells & Regenerat Med, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
[2] China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110001, Peoples R China
[3] China Med Univ, Dept Blood Transfus, Shengjing Hosp, Shenyang 110001, Peoples R China
[4] First Affiliated Hosp China Med, Dept Gen Practice, Shenyang, Peoples R China
关键词
Keratinocytes; Fibroblasts; Wound healing; Scarless; Fetus; Cytokines; FETAL SKIN; EXPRESSION; MIGRATION; FIBROSIS; WOUNDS; CELLS; EGF; RECEPTOR; MODEL; SCARS;
D O I
10.1016/j.burns.2014.12.013
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 lategestational 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-beta 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-beta 1, TGF-beta 2, TIMP-2 and TIMP-3, while precollagen 3, collagen 3, TGF-beta 3, and MMP-1, -2, -3, -9 and -14 were upregulated. In contrast, lategestational KCs exhibited downregulated TIMP-1, TIMP-2 and TIMP-3 levels, while collagen 1, TGF-beta 1, beta 2, TGF-beta 3, and MMP-2, -3, -9 and -14 were upregulated. Moreover, statistically significant differences in expression levels of precollagen 1, precollagen 3, collagen 1, TGF-beta 2, and -beta 3, 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 lategestational KCs. Therefore, the gestational age of KCs appears to have an important effect on scarless wound healing in the human fetus. 2015 Elsevier Ltd and ISBI. All rights reserved.
引用
收藏
页码:1064 / 1075
页数:12
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