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Ischemic Preconditioning-Induced SOCS-1 Protects Rat Intestinal Ischemia Reperfusion Injury via Degradation of TRAF6

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Abstract

Background

The inflammatory immune response plays an important role in mesenteric ischemia and ischemia–reperfusion injury. Toll-like receptor 4 (TLR4) is a critical receptor in transduction of the inflammatory response and plays an important role in intestinal homeostasis. Tumor necrosis factor receptor-associated factor 6 (TRAF6), known as a key adaptor protein downstream of TLR4, is involved in the inflammatory response by activating multiple apoptotic signaling pathways. However, mechanisms of the suppressor of cytokine signaling-1 (SOCS-1) in regulating cell inflammation and apoptosis are still obscure.

Objectives

To investigate the TLR4–TRAF6 signaling pathway in intestinal ischemia and reperfusion injury, as well as SOCS-1 expression after ischemic preconditioning in the rat intestine.

Methods

The small bowel ischemia, ischemia–reperfusion, and preconditioning models were induced using ligation of the superior mesenteric artery in male Sprague–Dawley rats; then, the mRNA and protein levels of TLR4, TRAF6, and SOCS-1 were analyzed using real-time PCR, Western blot, and immunohistochemistry, respectively.

Results

The expression of TLR4 and TRAF6 was gradually increased with increasing intestinal ischemia duration, but increased substantially after ischemia–reperfusion injury. After ischemic preconditioning, TLR4 and TRAF6 expressions decreased; however, expression of SOCS-1 and the TLR4–TRAF6 pathway inhibitor was increased.

Conclusion

These data show that ischemic preconditioning may induce the activation of SOCS-1 to inhibit the TLR4–TRAF6 signaling pathway, thereby playing a protective role in ischemia–reperfusion injury.

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Acknowledgments

This study was supported by the Department of Education Research Program of Sichuan Province, China, No. 10ZB120. I would like to extend my sincere thanks to all those who have helped me make this thesis possible and better. I gratefully acknowledge BioMed Proofreading LLC for the English copy editing of my manuscript.

Author information

Authors and Affiliations

  1. SouthWest Medical University Clinical Medicine, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People’s Republic of China

    Sheng-zhi Liu

  2. Department of Vascular Surgery, The Second People’s Hospital of Yibin, 96 North Street, Yi Bin, 644000, Sichuan Province, People’s Republic of China

    Sheng-zhi Liu

  3. Medical Research Center, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People’s Republic of China

    Xue-mei He

  4. Department of Pathology, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People’s Republic of China

    Xu Zhang

  5. Department of Biochemistry, SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People’s Republic of China

    Fan-cai Zeng

  6. Department of Vascular and Thyroid Surgery, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People’s Republic of China

    Fang Wang & Xiang-yu Zhou

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  1. Sheng-zhi Liu
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Correspondence to Xiang-yu Zhou.

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Conflict of interest

All authors concur with the publication in Digestive Diseases and Sciences. The data in this paper are new and have not been published previously, nor are under consideration for publication elsewhere, either completely, in part, or in another form. There are no conflicts of financial interest for all authors.

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Liu, Sz., He, Xm., Zhang, X. et al. Ischemic Preconditioning-Induced SOCS-1 Protects Rat Intestinal Ischemia Reperfusion Injury via Degradation of TRAF6. Dig Dis Sci 62, 105–114 (2017). https://doi.org/10.1007/s10620-016-4277-0

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  • DOI: https://doi.org/10.1007/s10620-016-4277-0

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