title: Rosiglitazone ameliorates senescence-like phenotypes in a cellular photoaging model.
abstract: BACKGROUND
  Rosiglitazone (RO), a second-generation thiazolidinedione used mainly in the treatment of non-insulin-dependent diabetes mellitus, has been discovered to be a high-affinity ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ). Several studies have revealed that PPAR-γ is also involved in the regulation of oxidative stress and chronic inflammation associated with aging process in vivo as well as with cellular senescence in vitro. We sought to investigate whether RO pretreatment will counteract the photoaging process using a well-established cellular photoaging model.
  
  
  METHODS
  Murine dermal fibroblasts (MDFs) were cultured in the absence or presence of RO for 48h, followed by exposure to repeated UVB irradiation. The senescent phenotypes were evaluated including cell viability, senescence-associated β-galactosidase (SA-β-gal) expression, cell morphology, ROS generation, cell cycle, production and degradation of extracellular matrix (ECM), and the potential mechanisms were discussed.
  
  
  RESULTS
  Pretreatment with RO (40μM) significantly decreased the staining intensity and the percentage of SA-β-gal-positive cells and reserved the elongated cell shape compared with UVB group. The cells pretreated with RO also showed decreased UVB-induced degradation of type I collagen by decreasing MMPs expressions. In addition, we observed counteraction of cell-cycle arrest and repression of UVB-induced p53 and p21 in the presence of RO. We further confirmed a significant decrease in ROS accumulation accompanied by an increase in catalase in RO group.
  
  
  CONCLUSIONS
  RO, a potent PPAR-γ activator, counteracts senescence-like phenotypes, including long-term growth arrest, flattened morphology, degradation of ECM and SA-β-gal-positive staining in MDFs by inhibiting the expression of MMPs and increasing the synthesis of catalase when administered to repeated UVB irradiation. The novel application of RO may lead to innovative and effective anti-photoaging therapies.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Bi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Hua Shan Hospital, Fu Dan University, Shanghai, China.
authors.forename: Ningwen
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hua Dong Hospital, Fu Dan University, Shanghai, China. Electronic address: tianyiliucn@126.com.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D002374:Catalase / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53; D000077154:Rosiglitazone; D002374:Catalase; D001616:beta-Galactosidase; D020782:Matrix Metalloproteinases
keywords: Dermal fibroblast; PPAR-γ; Photoaging; Rosiglitazone