TY - JOUR
T1 - Hierarchical control of interleukin 13 (IL-13) signals in lung fibroblasts by STAT6 and SOX11
AU - Mitamura, Yasutaka
AU - Nunomura, Satoshi
AU - Nanri, Yasuhiro
AU - Arima, Kazuhiko
AU - Yoshihara, Tomohito
AU - Komiya, Kosaku
AU - Fukuda, Shogo
AU - Takatori, Hiroaki
AU - Nakajima, Hiroshi
AU - Furue, Masutaka
AU - Izuhara, Kenji
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science KAK-ENHI Grants JP15K15372 and JP16H05343 (to K. I.) and by AstraZeneca (to K. I.). The authors declare that they have no conflicts of interest with the contents of this article. We thank Dr. Dovie R. Wylie for critical review of the manuscript. We also thank Miho Miyake and Maki Watanabe for technical assistance.
Publisher Copyright:
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2018/9/21
Y1 - 2018/9/21
N2 - Interleukin (IL)-13 is a signature cytokine of type 2 inflammation important for the pathogenesis of various diseases, including allergic diseases. Signal transducer and activator of transcription (STAT) 6 is a critical transcriptional factor for the IL-13 signals; however, it remains unknown how expression of the IL-13–induced genes is differentiated by the transcriptional machineries. In this study, we identified IL-13–induced transcriptional factors in lung fibroblasts using DNA microarrays in which SOX11 was included. Knockdown of SOX11 down-regulated expression of periostin and CCL26, both of which are known to be downstream molecules of IL-13, whereas enforced expression of SOX11 together with IL-13 stimulation enhanced expression of periostin. Moreover, we found that in DNA microarrays combining IL-13 induction and SOX11 knockdown there exist both SOX11-dependent and -independent molecules in IL-13–inducible molecules. In the former, many inflammation-related and fibrosis-related molecules, including periostin and CCL26, are involved. These results suggest that SOX11 acts as a trans-acting transcriptional factor downstream of STAT6 and that in lung fibroblasts the IL-13 signals are hierarchically controlled by STAT6 and SOX11.
AB - Interleukin (IL)-13 is a signature cytokine of type 2 inflammation important for the pathogenesis of various diseases, including allergic diseases. Signal transducer and activator of transcription (STAT) 6 is a critical transcriptional factor for the IL-13 signals; however, it remains unknown how expression of the IL-13–induced genes is differentiated by the transcriptional machineries. In this study, we identified IL-13–induced transcriptional factors in lung fibroblasts using DNA microarrays in which SOX11 was included. Knockdown of SOX11 down-regulated expression of periostin and CCL26, both of which are known to be downstream molecules of IL-13, whereas enforced expression of SOX11 together with IL-13 stimulation enhanced expression of periostin. Moreover, we found that in DNA microarrays combining IL-13 induction and SOX11 knockdown there exist both SOX11-dependent and -independent molecules in IL-13–inducible molecules. In the former, many inflammation-related and fibrosis-related molecules, including periostin and CCL26, are involved. These results suggest that SOX11 acts as a trans-acting transcriptional factor downstream of STAT6 and that in lung fibroblasts the IL-13 signals are hierarchically controlled by STAT6 and SOX11.
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U2 - 10.1074/jbc.RA117.001364
DO - 10.1074/jbc.RA117.001364
M3 - Article
C2 - 30076218
AN - SCOPUS:85054007382
SN - 0021-9258
VL - 293
SP - 14646
EP - 14658
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -