The involvement of leucine-rich α-2 glycoprotein in the progression of skin and lung fibrosis in bleomycin-induced systemic sclerosis model
The involvement of leucine-rich α-2 glycoprotein in the progression of skin and lung fibrosis in bleomycin-induced systemic sclerosis model
复制标题
富含亮氨酸的α-2糖蛋白参与博莱霉素诱导的系统性硬化症模型皮肤和肺纤维化的进展
DOI：
10.1080/14397595.2021.1883841
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Sano S.
中科院分区：
文献类型：
--
作者：
Nakajima H;Nakajima K;Serada S;Fujimoto M;Naka T;Sano S.
全身性硬化症（SSc）是一种自身免疫性疾病，其特征在于皮肤和内脏的纤维化。近年来研究表明，富含亮氨酸的α-2糖蛋白（LRG）在纤维化中作为转化生长因子-β（TGF-β）信号转导的调节剂发挥作用。我们旨在描述LRG在SSc模型和SSc patients.MethodsHistological分析进行LRG基因敲除（KO）和野生型（WT）小鼠的皮肤和肺博莱霉素给药后的效果。在注射期间测量血清LRG水平。对来自LRG KO和WT小鼠的皮肤和肺组织进行基因表达分析。此外，血清LRG水平测定SSc患者和健康controls.ResultsLRG基因敲除小鼠显示与减少真皮厚度，胶原沉积，磷酸化Smad 3表达博莱霉素后，在皮肤纤维化的抑制。在博莱霉素后，WT小鼠的血清LRG浓度显著增加。在LRG KO小鼠肺中还存在炎症和纤维化的抑制，这通过博来霉素后肺重量、胶原蛋白含量和磷酸化Smad 3表达的降低来指示。TGF-β和Smad 2/3的基因表达在LRG KO小鼠中显著降低。结论LRG通过TGF-β-Smad 3信号通路促进SSc的纤维化进程，LRG可能是SSc的生物标志物，也是SSc潜在的治疗靶点。
ObjectiveSystemc sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Recently, it has been shown that leucine-rich α-2 glycoprotein (LRG) functions as a modulator of transforming growth factor-β (TGF-β) signaling in fibrosis. We aimed to characterize the effect of LRG in SSc model and SSc patients.MethodsHistological analysis was performed on LRG knockout (KO) and wild type (WT) mouse in the skin and the lung after bleomycin administration. Serum LRG levels were measured during the injection period. Gene expression analysis of the skin and lung tissue from LRG KO and WT mice was performed. In addition, serum LRG levels were determined in SSc patients and healthy controls.ResultsLRG KO mice display an inhibition of fibrosis in the skin in association with a decrease of dermal thickness, collagen deposition, and phospho-Smad3 expression after bleomycin. Serum LRG concentration significantly increased in WT mice after bleomycin. There was also a suppression of inflammation and fibrosis in the LRG KO mouse lung indicated by a reduction of lung weight, collagen content, and phospho-Smad3 expression after bleomycin. Gene expressions of TGF-β and Smad2/3 were significantly reduced in LRG KO mice. Serum LRG levels in SSc patients were significantly higher than those in controls.ConclusionLRG promotes fibrotic processes in SSc model through TGF-β-Smad3 signaling, and LRG can be a biomarker for SSc in humans and also a potential therapeutic target for SSc.
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影响因子：
13.3
作者：
Takahashi, Takehiro;Asano, Yoshihide;Sato, Shinichi
通讯作者：
Sato, Shinichi
影响因子：
24.3
作者：
Lok, SS;Haider, Y;Egan, JJ
通讯作者：
Egan, JJ
影响因子：
4.4
作者：
Nakajima, Kimiko;Kanda, Takashi;Sano, Shigetoshi
通讯作者：
Sano, Shigetoshi
影响因子：
--
作者：
Takemoto N;Serada S;Fujimoto M;Honda H;Ohkawara T;Takahashi T;Nomura S;Inohara H;Naka T
通讯作者：
Naka T