title: Mesenchymal stem cell-conditioned medium improves the proliferation and migration of keratinocytes in a diabetes-like microenvironment.
abstract: The impairment of wound healing in diabetic patients is an important clinical problem. Proper keratinocyte migration and proliferation are the crucial steps during reepithelialization, and these steps may be impaired in diabetes mellitus (DM) due to hyperglycemia and chronic inflammation in wound site. In this study, we explored the effects of diabetes-like microenvironment with high glucose (HG) and intense inflammation on the migration and proliferation of keratinocytes in vitro. We found that the migration and proliferation of rat keratinocytes were reduced with HG and lipopolysaccharide (LPS) stimulation via Erk signaling pathway in a reactive oxygen species (ROS)-dependent manner. Nevertheless, mesenchymal stem cell-conditioned medium (MSC-CM) counteracts the effects of HG and LPS. Treatment of rat keratinocyte with MSC-CM decreased HG- and/or LPS-induced ROS overproduction. Furthermore, MSC-CM reversed the downregulation of phosphorylation of MEK1/2 and Erk 1/2, which was induced by HG and/or LPS without affecting total levels. Our results may provide a possible mechanism for delayed wound healing in DM and provide a foundation to develop MSC-CM as an alternative therapeutic strategy to ameliorate the poor wound-healing conditions.
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China Chinese PLA General Hospital Hainan Branch, Sanya, People's Republic of China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Li
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China Chinese PLA General Hospital Hainan Branch, Sanya, People's Republic of China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Hanren
authors.initials: H
authors.lastname: Dai
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Qingwang
authors.initials: Q
authors.lastname: Han
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Tong
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Chinese PLA General Hospital, Beijing, People's Republic of China fuxiaobing@vip.sina.com hanwdrsw69@yahoo.com.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned; D012313:RNA; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Erk signaling pathway; chronic inflammation; diabetes mellitus; hyperglycemia; mesenchymal stem cell–conditioned medium; nonhealing wound; oxidative stress