Extracellular matrix secreted by senescent fibroblasts induced by UVB promotes cell proliferation in HaCaT cells through PI3K/AKT and ERK signaling pathways
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.
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Document Type: Research Article
Affiliations: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, P.R. China
Publication date: January 1, 2008
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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