Abstract:
:UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report a novel role of transglutaminase 2 (TG2), a member of the TG enzyme family whose activities are critical for cornified envelope formation, in mediating UV-induced inflammation. Our results showed that TG2-deficient mice exhibited reduced inflammatory responses to UV irradiation, including reduced erythema, edema, dilation of blood vessels, inflammatory cell infiltration, and levels of inflammatory cytokines. Using primary mouse keratinocytes and HaCaT cells, we found that UV irradiation-induced cytokine production by activating TG2, but not by upregulating TG2 expression, and that ER calcium release triggered by the UV-induced activation of phospholipase C was required for TG2 activation. Moreover, TG2 activity enhanced p65 phosphorylation, leading to an increase in NF-κB transcriptional activity. These results indicate that TG2 is a critical mediator of cytokine expression in the UV-induced inflammatory response of keratinocytes, and suggest that TG2 inhibition might be useful for preventing UV-related skin disorders, such as photoaging and skin cancer caused by chronic UV exposure.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Lee SJ,Lee KB,Son YH,Shin J,Lee JH,Kim HJ,Hong AY,Bae HW,Kwon MA,Lee WJ,Kim JH,Lee DH,Jeong EM,Kim IGdoi
10.1038/cddis.2017.550subject
Has Abstractpub_date
2017-10-26 00:00:00pages
e3148issue
10issn
2041-4889pii
cddis2017550journal_volume
8pub_type
杂志文章abstract::MicroRNAs (miRNAs) deregulation is frequent in human gastric cancers (GCs), but the role of specific miRNAs involved in this disease remains elusive. MiR-22 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely ...
journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 已发布勘误
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