Human amniotic epithelial cells attenuate TGF-β1-induced human dermal fibroblast transformation to myofibroblasts via TGF-β1/Smad3 pathway.
Keloids are raised dermal scars that extend beyond the boundaries of the initial injury. To date, there is no treatment to erase scars completely in humans. Growing evidence has shown that the human amniotic epithelial cells have anti-fibrotic properties and can reduce the fibrosis of lung and liver. However, it is unknown whether and how they can influence human keloids. The aim of this study was to investigate whether factors secreted by human amniotic epithelial cells have anti-fibrotic effects on human keloids and to clarify the potential transduction mechanism.



Human amniotic epithelial cells were isolated and identified both with flow cytometry and immunofluorescent. The α-smooth muscle actin, collagen-I and III gene and protein expression of transforming growth factor (TGF)-β1-treated human adult dermal fibroblasts were partly abolished by human amniotic epithelial cells conditioned medium through stimulating the expression of matrix metalloproteinase (MMP). Furthermore, human amniotic epithelial cells conditioned medium effectively attenuated nuclear import of the Smad2/3 complex.



Soluble human leukocyte antigen G, a human amniotic epithelial cell-derived factor, significantly decreased collagen production in TGF-β1-induced human dermal fibroblasts, although the effect on collagen production was less than that of human amniotic epithelial cell-conditioned medium.



This study demonstrates that human amniotic epithelial cells conditioned medium could down-regulate the expression of fibrosis-related molecules by regulating MMP and tissue inhibitor of metalloproteinase levels, and suppress TGF-β1-induced fibroblast transition, in which the TGF-β1/Smad3 pathway is likely involved. These findings suggest that human amniotic epithelial cells are a potential therapeutic compound for the treatment of keloids.
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Bin
B
Zhao
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Jia-Qi
JQ
Liu
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Chen
C
Yang
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Zhao
Z
Zheng
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Qin
Q
Zhou
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Hao
H
Guan
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: linlinsu@fmmu.edu.cn.
Lin-Lin
LL
Su
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: hudhai@fmmu.edu.cn.
Da-Hai
DH
Hu
D000328:Adult; D000650:Amnion / Q000166:cytology* / Q000378:metabolism; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
D024042:Collagen Type I; D017077:Culture Media, Conditioned; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1
TGF-β1/Smad3 pathway; dermal fibroblasts; human amniotic epithelial cells; myofibroblast; transformation