title: Antiphotoaging effect of conditioned medium of dedifferentiated adipocytes on skin in vivo and in vitro: a mechanistic study.
abstract: Photoaging of skin occurs partially due to decreased synthesis and increased degradation of dermal collagen. Antiphotoaging therapy aims to counteract these effects. This study aimed to investigate whether secretory factors from dedifferentiated adipocytes (DAs) could alleviate photoaging in human dermal fibroblasts (HDFs) and in mice and to clarify the underlying mechanism. DAs were acquired and verified based on cellular biomarkers and multilineage differentiation potential. The concentrations of several cytokines in conditioned medium from DAs (DA-CM) were determined. In vivo pathological changes, collagen types I and III, and matrix metalloproteinase (MMP)-1 and -3 were evaluated following the injection of 10-fold concentrated DA-CM into photoaged mice. In vitro, the effect of DA-CM on stress-induced premature senescence in HDFs was investigated by 5-ethynyl-2'-deoxyuridine (EdU) staining and β-galactosidase staining. The influence of DA-CM and transforming growth factor-β1 (TGF-β1) on the secretion of collagen types I and III, MMP-1, and MMP-3 in HDFs was evaluated by ELISA. In vivo, we found that subcutaneously injected 10-fold concentrated DA-CM increased the expression of collagen types I and III. In vitro, DA-CM clearly mitigated the decreased cell proliferation and delayed the senescence status in HDFs induced by ultraviolet B (UVB). HDFs treated with DA-CM exhibited higher collagen types I and III secretion and significantly lower MMP-1 and MMP-3 secretion. The TGF-β1-neutralizing antibody could partially reduce the recovery effect. Our results suggest that DAs may be useful for aging skin and their effects are mainly due to secreted factors, especially TGF-β1, which stimulate collagen synthesis and alleviate collagen degradation in HDFs.
authors.affiliation: 1 Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jia-an
authors.initials: JA
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Shi-lei
authors.initials: SL
authors.lastname: Guo
authors.forename: Shen
authors.initials: S
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.forename: Bing-rong
authors.initials: BR
authors.lastname: Zhou
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D054337:Cell Dedifferentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism; D024043:Collagen Type II / Q000032:analysis / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012867:Skin / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects*
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D017077:Culture Media, Conditioned; D016207:Cytokines; D020781:Matrix Metalloproteinase 1