Modeling signaling pathways leading to wrinkle formation: Identification of the skin aging target.

ABSTRACT

Background: In the present scenario, wrinkle formation, prominent sign of skin ageing, is one of the most demanding areas of research. This burgeoning research demand to reduce, delay and restore the effects of skin ageing has led to the study of various signaling pathways leading to wrinkle formation. Wrinkles appear on skin due to influence of intrinsic and extrinsic factors on mitogenic reactions and signal transduction pathways. Aim: The aim of the present study is to analyze each protein involved in the signaling pathway leading to dilapidation of collagen and an attempt has been made to compare different signal transduction pathways to identify a common target for skin ageing. Methods: In the present work, bioinformatics tools have been used to extract information from already existing experimental data. The statistical techniques are used for further analysis and make useful predictions for skin ageing. Results: Stressors like UV irradiation, osmotic stress and heat shock have been reported to activate epidermal growth factor receptor, interleukin 1 receptor, tumor necrosis factor receptor, platelet-derived growth factor receptor and platelet activation factor receptor signaling pathways, which lead to the production of matrix metalloproteinases, collagen degradation and, consequently, wrinkle formation. When all the five signaling pathways were modeled, the c-jun part of the AP-1 transcription factor was found to be a common intermediate protein involved in all the signaling cascades. Moreover, it shows differential expression in the skin on response to stressors. Conclusion: We proposed c-jun to be the most potent target for drug designing against wrinkle formation.