title: Senescent dermal fibroblasts enhance stem cell migration through CCL2/CCR2 axis.
abstract: During aging, increases in the number of senescent cells are seen in various tissues. On the other hand, stem cells play crucial roles in tissue repair and homeostasis. Therefore, it is likely that stem cells give rise to new cells that replace senescent cells. However, how stem cells contribute to homeostasis in the dermis has not been elucidated. Here, we investigated the effects of factors secreted from senescent fibroblasts on stem cells. We found that senescent human dermal fibroblast (HDF) conditioned medium (CM) significantly enhanced stem cell migration compared with young HDF CM. The senescent HDF CM strongly secreted chemokine ligand 2 (CCL2). Furthermore, CCL2 was found to enhance stem cell migration, and the inhibition of CCR2, a receptor for CCL2, reduced stem cell migration. These results suggest that senescent fibroblasts recruit stem cells by secreting various factors and that the CCL2/CCR2 axis is one of the mechanisms underlying this phenomenon.
authors: Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Aichi, Japan.
authors: Shiro
authors: S
authors: Ohgo
authors: Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Aichi, Japan.|Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors: Seiji
authors: S
authors: Hasegawa
authors: Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Aichi, Japan.
authors: Yuichi
authors: Y
authors: Hasebe
authors: Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Aichi, Japan.
authors: Hiroshi
authors: H
authors: Mizutani
authors: Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Aichi, Japan.
authors: Satoru
authors: S
authors: Nakata
authors: Department of Applied Cell and Regenerative Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors: Hirohiko
authors: H
authors: Akamatsu
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology / Q000502:physiology; D018932:Chemokine CCL2 / Q000502:physiology*; D017077:Culture Media, Conditioned; D020405:Dermis / Q000166:cytology* / Q000276:immunology* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000502:physiology; D054390:Receptors, CCR2 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D054390:Receptors, CCR2
keywords: chemokine; dermal fibroblasts; mesenchymal stem cells; senescence; skin homeostasis