title: Extracellular matrix secreted by senescent fibroblasts induced by UVB promotes cell proliferation in HaCaT cells through PI3K/AKT and ERK signaling pathways.
abstract: Chronic exposure to solar ultraviolet radiation (UV) induces photoaging, and ultimately photocarcinogenesis. Senescent human skin fibroblasts (HSFs) in UVB stress-induced premature senescence (UVB-SIPS) share a similar extracellular matrix (ECM) phenotype with other types of senescent fibroblast. ECM from senescent fibroblasts induced by a variety of stresses has been shown to promote preneoplastic and neoplastic epithelial cell growth, a potential mechanism in carcinogenesis. We undertook this study to explore whether the extracellular matrices from UVB-induced senescent fibroblasts have any effect on the proliferation of HaCaT cells. The results showed that ECM secreted from HSFs in UVB-SIPS has 13.15 and 29.27% more stimulatory effect on proliferation than ECM secreted from presenescent HSFs and non-ECM, respectively. ECM from fibroblasts in UVB-SIPS activates FAK, ERK, and AKT in HaCaT cells. ERK and PI3K/AKT inhibitors inhibit ECM-induced ERK, AKT activation and cell proliferation. Cytochalasin D, a destructive agent of the cytoskeleton, inhibits ECM-induced FAK activation and cell proliferation in HaCaT cells. Collectively, we conclude that ECM secreted from HSFs in UVB-SIPS promotes cell proliferation via ERK and PI3K/AKT pathways and modulation of FAK and cytoskeletal proteins in HaCaT cells. Pharmacological manipulation of those signaling components may lead to the prevention and treatment of skin cancer induced by chronic solar exposure.
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Chen
authors.forename: Jiping
authors.initials: J
authors.lastname: Xia
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Weiling
authors.initials: W
authors.lastname: Sun
authors.forename: Xiuzu
authors.initials: X
authors.lastname: Song
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Xiang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bi
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology* / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D015595:Skin Aging / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D051417:Focal Adhesion Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt