title: Estrogen Accelerates Cutaneous Wound Healing by Promoting Proliferation of Epidermal Keratinocytes via Erk/Akt Signaling Pathway.
abstract: BACKGROUND
  Previous studies have established that estrogen is capable of accelerating cutaneous wound healing through multiple mechanisms, one of which involves affecting keratinocytes biological properties, such as migration, proliferation, etc. This study aims to reveal the underlying molecular mechanisms of estrogen promoting epidermal keratinocytes proliferation. Method &amp;
  
  
  RESULTS
  We found that compared with female mice with a normal estrous cycle, female mice with their ovaries removed before puberty exhibited a delayed cutaneous wound healing, thinner epidermis, and significantly fewer proliferating cell nuclear antigen (PCNA)-positive keratinocytes. Moreover, a significant increase in HaCaT proliferation was detected by a CCK8 assay when treated with 17 β-estradiol compared with those treated with control vehicle. Consistent with the results of the CCK8 assay, flow cytometry indicated a high proportion of 17 β-estradiol-treated HaCaT cells in S phase compared with vehicle-treated cells. Western blot analysis demonstrated the activation of Akt, Erk and upregulation of PCNA in HaCaT cells treated with 17 β-estradiol. Interestingly, Erk activation occurred prior to Akt activation. Upregulation of PCNA expression, elevated proliferation and high S phase fraction of HaCaT cell by 17 β-estradiol could be reversed by an Akt or Erk inhibitor. Moreover, Erk inhibition reversed 17 β-estradiol-induced Akt activation, whereas an Akt inhibitor exhibited no effect on Erk, further suggesting that Erk was on the upstream while Akt on the downstream of the signaling pathway.
  
  
  CONCLUSIONS
  This study demonstrates that one of the critical mechanisms underlying 17 β-estradiol promoting skin wound healing is through regulation of keratinocyte proliferation via Erk/Akt signaling pathway.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Key Laboratory for Proteomics Disease, Institute of Burn Research, Southwest Hospital, the Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Yajie
authors.initials: Y
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: You
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004967:Estrogens; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt