期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 99, 期 -, 页码 140-146出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2018.04.007
关键词
Mesencephalic astrocyte-derived neurotrophic factor; Endoplasmic reticulum stress; X-box binding protein-1; Hepatitis B
资金
- National Natural Science Foundation of China [81173074, 81372576, 91129729]
As an endoplasmic reticulum (ER) stress-related protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) is involved in inflammatory diseases, such as rheumatoid arthritis. However, the mechanisms of the transcriptional regulation of MANF is still undefined. Here, we showed that MANF expression was upregulated in hepatitis B tissues and hepatoma cells, and positively correlated with the spliced X-box binding protein-1 (XBP1s). Both overexpression of XBP1s and tunicamycin treatment were able to enhance MANF transcription. On the contrary, inhibition of XBP1 splicing by IRE1 alpha endonuclease inhibitor or knockdown of XBP1s with siRNA attenuated MANF expression. Two ER stress-responsive elements (ERSE) were found in the promoter region of MANF (ERSE I and ERSE II). The chromatin immunoprecipitation and reporter gene assay showed that XBP1s mainly binds to ERSE I to promote MANF transcription. Moreover, MANF was found to interact with XBP1s to enhance its own expression. Our findings uncover a new mechanism of ERSE-dependent transcriptional regulation of MANF, as well as a key role of XBP1s in promoting the MANF expression.
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