title: Dynamic Expression of Novel MiRNA Candidates and MiRNA-34 Family Members in Early- to Mid-Gestational Fetal Keratinocytes Contributes to Scarless Wound Healing by Targeting the TGF-β Pathway.
abstract: BACKGROUND
  Early- to mid-gestational fetal mammalian skin wounds heal rapidly and without scarring. Keratinocytes (KCs) have been found to exert important effects on the regulation of fibroblasts. There may be significant differences of gestational fetal KCs at different ages. The advantages in early- to mid-gestational fetal KCs could lead to fetal scarless wound healing.
  
  
  METHODS
  KCs from six human fetal skin samples were divided into two groups: a mid-gestation group (less than 28 weeks of gestational age) and a late-gestation group (more than 28 weeks of gestational age). RNA extracted from KCs was used to prepare a library of small RNAs for next-generation sequencing (NGS). To uncover potential novel microRNA (miRNAs), the mirTools 2.0 web server was used to identify candidate novel human miRNAs from the NGS data. Other bioinformatical analyses were used to further validate the novel miRNAs. The expression levels of the miRNAs were further confirmed by real-time quantitative RT-PCR.
  
  
  RESULTS
  A total of 61.59 million reads were mapped to 1,170 known human miRNAs in miRBase. Among a total of 202 potential novel miRNAs uncovered, 106 candidates have a higher probability of being novel human miRNAs. A total of 110 miRNAs, including 22 novel miRNA candidates, were significantly differently expressed between mid- and late-gestational fetal KCs. Thirty-three differentially expressed miRNAs and miR-34 family members are correlated with the transforming growth factor-β (TGF-β) pathway.
  
  
  CONCLUSIONS
  Taken together, our results provide compelling evidence supporting the existence of 106 novel miRNAs and the dynamic expression of miRNAs that extensively targets the TGF-β pathway at different gestational ages in fetal KCs. MiRNAs showing altered expression at different gestational ages in fetal KCs may contribute to scarless wound healing in early- to mid-gestational fetal KCs, and thus may be new targets for potential scar prevention and reduction therapies.
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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Blood Transfusion, Shengjing Hospital of China Medical University, 39 Huaxiang Street, Tiexi District, Shenyang City 110004, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Lang
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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of General Practice, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, Liaoning Province, 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, 77 Puhe Street, Shenbei New District, Shenyang City 110013, Liaoning Province, China.
authors.forename: Xining
authors.initials: X
authors.lastname: Pang
mesh_terms: D002478:Cells, Cultured; D002921:Cicatrix; D005260:Female; D005333:Fetus / Q000166:cytology*; D005865:Gestational Age; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism*; D011247:Pregnancy; D012867:Skin / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D016212:Transforming Growth Factor beta