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TNF-α Regulates ITGβ1 and SYND4 Expression in Nucleus Pulposus Cells: Activation of FAK/PI3K Signaling

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Abstract

Integrins can function synergistically with syndecan-4 (SYND4) and bind to the fibronectin (FN) matrix, resulting in the regulation of tissue regeneration. This study aimed to explore the effects of TNF-α on the formation of FN/ITGβ1/SYND4 complex and the relative mechanism in NP cells. The expression of FN-ITG-SYND4 at the cellular level under TNF-α stimulation was detected by immunofluorescent staining, western blotting, and RT-PCR. ITGβ1 is a crucial component of ITG FN-induced FAK signaling, which was detected using dual mode. And, the involved signaling down stream pathways were also detected. FN is a preferred adhesion substrate for NP cells and that integrin β1 (ITGβ1) and SYND4 work synergistically during ECM engagement in a focal adhesion kinase (FAK)-dependent fashion. The PI3k/Akt pathway is obviously down-regulated, resulting in decreased adherence capacity and increased anoikis. TNF-α induction could weaken FAK activity and downstream levels of phospho-PI3K and Akt, resulting in decreased adherence capacity and increased apoptosis. Thus, TNF-α is essential for the formation of FN/ITGβ1/SYND4 complex in NP cells and further elucidates the inflammatory mechanism of NP cells degeneration.

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Funding

This study was supported by grants from the financial support of the National Science Foundation of China (NSFC, U1603121, 81201393, 81272025, 81541056; 2013YGYL015, WJ2017Z017).

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Author notes

  1. Xinghuo Wu and Suyun Li contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China

    Xinghuo Wu, Suyun Li, Kun Wang, Wenbin Hua, Shuai Li, Yu Song, Yukun Zhang, Shuhua Yang & Cao Yang

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  1. Xinghuo Wu
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  2. Suyun Li
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  3. Kun Wang
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  4. Wenbin Hua
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  6. Yu Song
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  7. Yukun Zhang
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  8. Shuhua Yang
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  9. Cao Yang
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Correspondence to Cao Yang.

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This study was reviewed and approved by the Ethics Committee of Tongji Medical College; written informed consent was obtained from all patients.

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Wu, X., Li, S., Wang, K. et al. TNF-α Regulates ITGβ1 and SYND4 Expression in Nucleus Pulposus Cells: Activation of FAK/PI3K Signaling. Inflammation 42, 1575–1584 (2019). https://doi.org/10.1007/s10753-019-01019-9

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  • DOI: https://doi.org/10.1007/s10753-019-01019-9

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