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Transforming growth factor-β1 suppress pentraxin-3 in human orbital fibroblasts

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Abstract

Purpose

Transforming growth factor-β (TGF-β), recognized as a crucial factor in regulating fibrosis and tissue remodeling, plays a role in thyroid-associated ophthalmopathy (TAO). Pentraxin-3 (PTX3), a member of pentraxins, was recently implicated in many autoimmune and fibrotic diseases. Thus, we hypothesize if there is a potential correlation between TGF-β and PTX3 in orbital fibroblasts (OFs).

Methods

Several strains of OFs obtained from patients with TAO (n = 8) and healthy donors (n = 3) were established as the study model. Recombinant TGF-β1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-β and siRNA knockdown of Smads were utilized.

Results

We found that TGF-β1 can reduce PTX3 protein expression in OFs. We also demonstrated that this downregulation was mediated at a pretranslational level, and PTX3 mRNA was inhibited in a time- and concentration-dependent manner by TGF-β1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-β receptor complex (type I:type II) and the Smad2/3-Smad4-dependent pathway are essential for TGF-mediated PTX3 repression.

Conclusion

These findings indicated that TGF-β1 can inhibit PTX3 expression in human OFs, which may participate in inflammation and fibrosis in patients with TAO and provide a potential target for the antifibrotic treatment.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (no. 81770959 and no. 81570885) and Shanghai Municipal Commission of Health and Family Planning (no. 201640215).

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Authors and Affiliations

  1. Department of Ophthalmology, Changzheng Hospital of Naval Medicine University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China

    Jiale Diao, Xinxin Chen, Pei Mou & Ruili Wei

  2. Department of Ophthalmology, Zhabei Central Hospital, Jingan District, 619 Zhonghua Xin Road, Shanghai, 200070, China

    Lihong Jiang

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  1. Jiale Diao
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Contributions

J.D. and X.C. made equal contributions to this work. The study was designed by J.D., L.J., and P.M. X.C. collected the samples and data. J.D. and X.C. performed the experiments. J.D. wrote the manuscript, and R.W. approved the submitted manuscript.

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Correspondence to Ruili Wei.

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Diao, J., Chen, X., Jiang, L. et al. Transforming growth factor-β1 suppress pentraxin-3 in human orbital fibroblasts. Endocrine 70, 78–84 (2020). https://doi.org/10.1007/s12020-020-02307-3

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