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SOCS3 Silencing Promotes Activation of Vocal Fold Fibroblasts via JAK2/STAT3 Signaling Pathway

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Abstract

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulatory protein that has been identified as a key inhibitory regulator of JAK/STAT signaling pathway. However, the mutual regulatory relationship between SOCS3 and JAK2/STAT3 signaling pathway after vocal fold injury remains unclear. In this study, we used small interfering RNA (siRNA) to investigate the mechanism of SOCS3 regulating of fibroblasts through JAK2/STAT3 signaling pathway after vocal fold injury. Our data shows that SOCS3 silencing promotes the transformation of normal vocal fold fibroblasts (VFFs) into an fibrotic phenotype and activates the JAK2/STAT3 signaling pathway. JAK2 silencing significantly inhibits the increase in type I collagen and α-smooth muscle actin (α-SMA) secretion in VFFs induced by TGF-β but has no significant effect on normal VFFs. The silencing of SOCS3 and JAK2 reverses the fibrotic phenotype of VFFs induced by SOCS3 silencing. Therefore, we suggest that SOCS3 can affect the activation of vocal fold fibroblasts by regulating the JAK2/STAT3 signaling pathway after vocal fold injury. It provides a new insight for promoting the repair of vocal fold injury and preventing the formation of fibrosis.

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Acknowledgements

The authors are appreciative to Professor Yan Zhang (School of Life Sciences, Peking University) for her inspiring thoughts and helpful suggestions regarding the project and the manuscript.

Funding

This work was supported by programs of the National Natural Science Foundation of China (82171124; 81870709) and Beijing Natural Science Foundation (7212014).

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology-Head and Neck Surgery, Ministry of Education of China, 1 Dongjiaominxiang, 100730, Beijing, China

    Xueyan Li, Rong Hu, Haizhou Wang & Wen Xu

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  1. Xueyan Li
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  2. Rong Hu
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  3. Haizhou Wang
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  4. Wen Xu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Xueyan Li, Rong Hu, and Haizhou Wang. The first draft of the manuscript was written by Xueyan Li, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Wen Xu.

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Li, X., Hu, R., Wang, H. et al. SOCS3 Silencing Promotes Activation of Vocal Fold Fibroblasts via JAK2/STAT3 Signaling Pathway. Inflammation 46, 1318–1331 (2023). https://doi.org/10.1007/s10753-023-01810-9

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  • DOI: https://doi.org/10.1007/s10753-023-01810-9

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