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A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis

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Abstract

Leukemia inhibitory factor (LIF) is a member of IL-6 family, which serves as a potent chemoattractant for neutrophils as well as a potent angiostatic factor. LIF has been implicated in various autoimmune inflammatory diseases, but its role still remains elusive in systemic sclerosis (SSc). Therefore, we investigated the potential role of LIF in the development of SSc by evaluating the clinical correlation of serum LIF levels, the expression of LIF and its receptors in skin samples, and in vitro experiments with human dermal microvascular endothelial cells. Serum LIF levels were significantly decreased in patients with SSc, especially in those with disease duration of < 1 year compared with healthy controls. As for clinical correlation, SSc patients with digital ulcers exhibited serum LIF levels significantly lower than those without. In immunohistochemistry, the expression of LIF and its receptors, LIF receptor and gp130, was remarkably decreased in dermal blood vessels of SSc lesional skin relative to those of healthy control skin. Furthermore, gene silencing of transcription factor Fli1, whose deficiency is involved in the development of SSc vasculopathy, suppressed the expression of LIF, LIF receptor, and gp130 and Fli1 bound to the promoters of those genes in human dermal microvascular endothelial cells. Collectively, these results suggest that decreased serum LIF levels may be associated with vasculopathy in SSc and that Fli1 deficiency may contribute to the inhibition of LIF-dependent biological effects on SSc endothelial cells by suppressing the expression of LIF, LIF receptor, and gp130.

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Acknowledgements

This work was supported by a Grant for Research on Intractable Diseases from the Ministry of Health, Labour, and Welfare of Japan.

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  1. Takashi Taniguchi, Takuya Miyagawa contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Takashi Taniguchi, Takuya Miyagawa, Zenshiro Tamaki, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Ayumi Yoshizaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato & Yoshihide Asano

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  1. Takashi Taniguchi
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Taniguchi, T., Miyagawa, T., Tamaki, Z. et al. A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis. Arch Dermatol Res 309, 833–842 (2017). https://doi.org/10.1007/s00403-017-1786-4

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  • DOI: https://doi.org/10.1007/s00403-017-1786-4

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