title: Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways.
abstract: Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Plastic Surgery, Shenyang Northern Hospital, Shenyang, Liaoning, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shu-Yue
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shi-Chao
authors.initials: SC
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. linlinsu@fmmu.edu.cn.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Su
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. hudhai@fmmu.edu.cn.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
mesh_terms: D000328:Adult; D000650:Amnion / Q000166:cytology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Amniotic epithelial stem cells; Keratinocytes; Signaling pathways; Wound healing