A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis.
A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis.
复制标题
LIF、LIFR 和 gp130 水平降低可能与系统性硬化症相关的血管病变有关。
DOI：
10.1007/s00403-017-1786-4
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Asano Y.
中科院分区：
文献类型：
--
作者：
sclerosis. Taniguchi T;Miyagawa T;Tamaki Z;Nakamura K;Yamashita T;Saigusa R;Takahashi T;Toyama T;Ichimura Y;Yoshizaki A;Tada Y;Sugaya M;Kadono T;Sato S;Asano Y.
白血病抑制因子（LIF）是IL-6家族的成员，是一种强有力的中性粒细胞趋化因子和血管生成抑制因子。LIF与多种自身免疫性炎症性疾病有关，但其在系统性硬化症（SSc）中的作用仍然难以捉摸。因此，我们通过评估血清LIF水平、皮肤样品中LIF及其受体的表达以及人真皮微血管内皮细胞的体外实验的临床相关性，研究了LIF在SSc发展中的潜在作用。与健康对照组相比，SSc患者血清LIF水平显著降低，尤其是病程< 1年的患者。至于临床相关性，SSc患者手指溃疡表现出血清LIF水平显着低于那些没有。在免疫组化中，LIF及其受体，LIF受体和gp 130，在SSc病变皮肤的真皮血管中的表达相对于健康对照皮肤显著降低。此外，转录因子Fli 1的基因沉默，其缺陷参与SSc血管病变的发展，抑制LIF，LIF受体，和gp 130和Fli 1结合到这些基因的启动子在人真皮微血管内皮细胞的表达。总的来说，这些结果表明，降低血清LIF水平可能与SSc血管病变和Fli 1缺陷可能有助于抑制LIF依赖性生物学效应SSc内皮细胞通过抑制LIF，LIF受体和gp 130的表达。
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.