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Pyruvate Kinase M2 Regulates Apoptosis of Intestinal Epithelial Cells in Crohn’s Disease

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Abstract

Background

Pyruvate kinase M2 (PKM2), a key glycolytic enzyme, is involved in multiple cellular processes including apoptosis. Recently increased fecal PKM2 has been found in Crohn’s disease (CD), but little is known regarding its function in the pathophysiology of the disease.

Aim

The intestinal expression of PKM2 and its involvement in CD was investigated.

Methods

Pyruvate kinase M2 expression in mucosal biopsies from patients with CD and normal controls was detected by immunohistochemistry. A murine model of colitis induced by trinitrobenzenesulphonic acid (TNBS) was established and expression of PKM2, B cell lymphoma-extra large (Bcl-xl), active caspase-3 as well as cleaved poly (ADP-ribose) polymerase (PARP) was examined for association of PKM2 with intestinal epithelial cell (IEC) apoptosis. Furthermore, we treated human IEC line HT-29 by tumor necrosis factor-α (TNF-α) and used RNA interference to analyze the role of PKM2 in IEC apoptosis.

Results

Intestinal expression of PKM2 was higher in patients with CD compared with normal controls mainly locating in IECs. In TNBS-induced colitis, up-regulation of PKM2 was accompanied by the elevated expression of Bcl-xl, active caspase-3, and cleaved PARP. PKM2 was co-localized with active caspase-3 in IECs marked by E-cadherin, suggesting its role in IEC apoptosis. Expression of PKM2 and Bcl-xl in TNF-α-induced HT-29 cells was increased, while TNF-α had no effect on cellular localization of PKM2. Furthermore, knockdown of PKM2 by siRNA could inhibit expression of Bcl-xl but enhance apoptosis in TNF-α-treated HT-29 cells.

Conclusion

The up-regulation of PKM2 might protect IECs against apoptosis possibly through Bcl-xl in CD, indicating its important role in the pathophysiology of CD.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 81201252), the Jiangsu Province’s Key Provincial Talents Program (RC2011079), and the Project of the six talent summit of Jiangsu Province (2009-B1-002).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Qiyun Tang & Jian’an Bai

  2. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China

    Qianqian Ji, Weiwei Xia, Liren Li & Runzhou Ni

  3. Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China

    Yongwei Qin

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  1. Qiyun Tang
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Correspondence to Runzhou Ni or Yongwei Qin.

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Qiyun Tang and Qianqian Ji have contributed equally to this study.

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Tang, Q., Ji, Q., Xia, W. et al. Pyruvate Kinase M2 Regulates Apoptosis of Intestinal Epithelial Cells in Crohn’s Disease. Dig Dis Sci 60, 393–404 (2015). https://doi.org/10.1007/s10620-014-3189-0

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  • DOI: https://doi.org/10.1007/s10620-014-3189-0

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