IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation
| Autor: | Krishnamurthy Natarajan, Sonali Bajaj, Hemanta Kumar Kar, Vinaya Vijayan, Prachi P. Dani, Rajni Rani, Parul Ganju, Kritika Kirty, Archana Singh, Vivek T. Natarajan, Chetan Gadgil, Shraddha Puntambekar, Shalini Yadav, Rajesh S. Gokhale |
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| Rok vydání: | 2014 |
| Předmět: |
Mice
Knockout Regulation of gene expression Melanosomes Multidisciplinary Transcription Genetic integumentary system Regulator Cellular homeostasis Skin Pigmentation Human skin Biological Sciences Biology Phenotype Cell biology Interferon-gamma Mice Microscopy Electron Transmission Cell Line Tumor Immunology Animals Melanocytes Signal transduction Transcription factor Signal Transduction Melanosome |
| Zdroj: | Proceedings of the National Academy of Sciences. 111:2301-2306 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1304988111 |
| Popis: | Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UV-induced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders. |
| Databáze: | OpenAIRE |
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