التفاصيل البيبلوغرافية
| العنوان: |
Retinal pigment epithelium transcriptome analysis in chronic smoking reveals a suppressed innate immune response and activation of differentiation pathways. |
| المؤلفون: |
Wang, Lei1 (AUTHOR) lwang9@jhmi.edu, Kaya, Koray D.2 (AUTHOR) koraydogan.kaya@nih.gov, Kim, Sujung1 (AUTHOR) sjun6@jhmi.edu, Brooks, Matthew J.2 (AUTHOR) brooksma@nei.nih.gov, Wang, Jie1 (AUTHOR) jwang240@jhmi.edu, Xin, Ying1 (AUTHOR) yingxinac@gmail.com, Qian, Jiang1 (AUTHOR) jiang.qian@jhmi.edu, Swaroop, Anand2 (AUTHOR) swaroopa@nei.nih.gov, Handa, James T.1 (AUTHOR) jthanda@jhmi.edu |
| المصدر: |
Free Radical Biology & Medicine. Aug2020, Vol. 156, p176-189. 14p. |
| مصطلحات موضوعية: |
*RHODOPSIN, *INTERFERON gamma, *IMMUNE response, *CIGARETTE smoke, *SMOKING, *IMMUNOSUPPRESSION |
| مستخلص: |
Cigarette smoking, a powerful mixture of chemical oxidants, is the strongest environmental risk factor for developing age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western societies. Despite intensive study, the full impact of smoking on the retinal pigment epithelium (RPE), a central cell type involved in AMD pathobiology, remains unknown. The relative contribution of the known dysfunctional pathways to AMD, at what stage they are most pathogenic, or whether other processes are relevant, is poorly understood, and furthermore, whether smoking activates them, is unknown. We performed global RNA-sequencing of the RPE from C57BL/6J mice exposed to chronic cigarette smoke for 6 months to identify potential pathogenic and cytoprotective pathways. The RPE transcriptome induced by chronic cigarette smoking exhibited a mixed response of marked suppression of the innate immune response including type I and II interferons and upregulation of cell differentiation and morphogenic gene clusters, suggesting an attempt by the RPE to maintain its differentiated state despite smoke-induced injury. Given that mice exposed to chronic smoke develop early features of AMD, these novel findings are potentially relevant to the transition from aging to AMD. Image 1 • Chronic smoking suppressed the immune response including interferons in the RPE. • Cell differentiation genes were also upregulated as a compensatory response. • STAT1 and STAT3 were reciprocally activated to regulate the extracellular matrix. • Matrix alterations to Bruch's membrane are early events in AMD. • The transcriptome to smoke is complex with both impaired and compensatory responses. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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