title: Anti-photoaging potential of Botulinum Toxin Type A in UVB-induced premature senescence of human dermal fibroblasts in vitro through decreasing senescence-related proteins.
abstract: This study was aimed to evaluate the anti-photoaging effects of Botulinum Toxin Type A (BoNTA) in Ultraviolet B-induced premature senescence (UVB-SIPS) of human dermal fibroblasts (HDFs) in vitro and the underlying mechanism. We established a stress-induced premature senescence model by repeated subcytotoxic exposures to Ultraviolet B (UVB) irradiation. The aging condition was determined by cytochemical staining of senescence-associated β-galactosidase (SA-β-gal). The tumor suppressor and senescence-associated protein levels of p16(INK-4a), p21(WAF-1), and p53 were estimated by Western blotting. The G1 phase cell growth arrest was analyzed by flow cytometry. The mRNA expressions of p16, p21, p53, COL1a1, COL3a1, MMP1, and MMP3 were determined by real-time PCR. The level of Col-1, Col-3, MMP-1, and MMP-3 were determined by ELISA. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with BoNTA demonstrated a decrease in the expression of SA-β-gal, a decrease in the level of tumor suppressor and senescence-associated proteins, a decrease in the G1 phase cell proportion, an increase in the production of Col-1 and Col-3, and a decrease in the secretion of MMP-1 and MMP-3, in a dose-dependent manner. Taken together, these results indicate that BoNTA significantly antagonizes premature senescence induced by UVB in HDFs in vitro, therefore potential of intradermal BoNTA injection as anti-photoaging treatment still remains a question.
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Felicia
authors.initials: F
authors.lastname: Permatasari
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jia-an
authors.initials: JA
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: bingrong.2002@163.com.
authors.forename: Bing-rong
authors.initials: BR
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: daniluo2013@njmu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
mesh_terms: D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000528:radiation effects; D003094:Collagen / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D003094:Collagen; D001616:beta-Galactosidase; D020782:Matrix Metalloproteinases; D019274:Botulinum Toxins, Type A
keywords: Botulinum Toxin Type A; Collagen; G1 arrest; Photoaging; SA-β-gal; Stress-induced premature senescence; UVB