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Immunologic Research

, Volume 62, Issue 2, pp 198–212 | Cite as

Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation

  • Liren Li
  • Xianjing Miao
  • Runzhou Ni
  • Xiaobing Miao
  • Liang Wang
  • Xiaodan Gu
  • Lijun Yan
  • Qiyun TangEmail author
  • Dongmei ZhangEmail author
Article

Abstract

Epithelial-specific ETS-1 (ESE1), also named as ELF3, ERT and ESX, belonging to the ETS family of transcription factors, exerts multiple activities in inflammation, epithelial differentiation and cancer development. Previous data demonstrated that ESE1 synergizes with NF-κB to induce inflammation and drive tumor progress, and the nuclear translocation of ESE1 promotes colon cells apoptosis. However, the expression and biological functions of ESE1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that ESE1/ELF3 was over-expressed in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced colitis mouse models, we observed the up-regulation of ESE1/ELF3 accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators [phosphorylated NF-κB p65 subunit (p-p65) and p-IκB] in colitis IECs. Increased co-localization of ESE1/ELF3 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of ESE1/ELF3 in NF-κB-mediated IEC apoptosis in UC. Employing the TNF-α-treated HT-29 cells as an IEC apoptosis model, we confirmed the positive correlation of ESE1/ELF3 with NF-κB activation and caspase-dependent IEC apoptosis in vitro. Immunoprecipitation and immunofluorescence assay revealed the physical interaction and increased nuclear translocation of ESE1/ELF3 and the NF-κB p65 subunit in TNF-α-treated HT-29 cells. Knocking ESE1/ELF3 down by siRNA significantly alleviated TNF-α-induced NF-κB activation and cellular apoptosis in HT-29 cells. Taken together, our data suggested that ESE1/ELF3 may promote the UC progression via accelerating NF-κB activation and thus facilitating IEC apoptosis.

Keywords

Ulcerative colitis Epithelial-specific ETS-1 Intestinal epithelial cell Apoptosis 

Notes

Acknowledgments

This work was supported by National Basic Research Program of China (973 Program, No. 2012CB822104); National Natural Science Foundation of China (81201252, 81470806, 81171140, 81472272); Nantong City Social Development Projects funds (HS2012032); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); the Natural Science Foundation of Jiangsu Province Grant (BK20141496).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Liren Li
    • 1
  • Xianjing Miao
    • 1
  • Runzhou Ni
    • 1
  • Xiaobing Miao
    • 5
  • Liang Wang
    • 1
  • Xiaodan Gu
    • 1
  • Lijun Yan
    • 4
  • Qiyun Tang
    • 4
    Email author
  • Dongmei Zhang
    • 2
    • 3
    Email author
  1. 1.Department of GastroenterologyAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Department of Pathogen Biology, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  3. 3.Jiangsu Province Key Laboratory for Inflammation and Molecular Drug TargetNantong UniversityNantongPeople’s Republic of China
  4. 4.Department of GastroenterologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingPeople’s Republic of China
  5. 5.Department of PathologyAffiliated Cancer Hospital of Nantong UniversityNantongPeople’s Republic of China

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