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TRIM27 promotes IL-6-induced proliferation and inflammation factor production by activating STAT3 signaling in HaCaT cells.

Am J Physiol Cell Physiol. 2020 Feb 01;318(2):C272-C281. doi:10.1152/ajpcell.00314.2019. Epub 2019 Nov 20
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摘要


The signaling pathway is required for the development of psoriatic lesions, and tripartite motif-containing 27 (TRIM27) is a protein inhibitor of activated (PIAS3)-interacting protein that could modulate IL-6-induced duanyu18133 activation. However, whether TRIM27 is associated with the IL-6/duanyu18133 signaling pathway in psoriasis remains enigmatic. TRIM27 expression and gene set enrichment analysis in patients with psoriasis were determined using bioinformatics. Human keratinocyte HaCaT cells treated with recombinant protein IL-6 (rh-IL-6) were transduced with lentivirus silencing TRIM27 and/or PIAS3 or, otherwise, transduced with lentivirus expressing TRIM27 and/or lentivirus silencing or MG132, a proteasome-specific protease inhibitor. Cell proliferation and inflammation factor production were measured using Cell Counting Kit-8 and ELISA, respectively. TRIM27, proliferation marker protein Ki-67 (Ki67), duanyu18133, and PIAS3 expressions were determined using real-time quantitative PCR, immunofluorescence staining, or Western blot analysis. Coimmunoprecipitation combined with ubiquitination analysis was performed to explore the interaction between TRIM27 and PIAS3. In the present study, TRIM27 expression was increased in psoriatic lesions, associated with the IL-6 signaling pathway, and induced by rh-IL-6 in a time-dependent manner. The increased cell proliferation, inflammation factor production, and expression of Ki67 and of relative to duanyu18133 induced by rh-IL-6 and TRIM27 overexpression were significantly inhibited by TRIM27 silencing and duanyu18133 silencing, respectively. More importantly, TRIM27 interacted with PIAS3, and its overexpression promoted PIAS3 ubiquitination in HaCaT cells. PIAS3 silencing also significantly promoted TRIM27-dependent and IL6-induced duanyu18133 activation, cell proliferation, and inflammation factor production. In conclusion, our results highlight that TRIM27 expression is significantly increased by IL-6 and suggest a mechanism for regulation of inflammation and proliferation-associated development of psoriasis.

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