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Abstract：
Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.
摘要：
成纤维细胞起源于骨髓单核细胞谱系，参与肺纤维化的发病机制。提供纤维细胞综合图片的研究仍然有限。Cofilin-1(CFL-1)是调节细胞增殖的重要蛋白,迁移和分化。CFL-1能否诱导单核细胞分化为纤维细胞，促进肺纤维化进程尚不清楚。与健康对照组相比，特发性肺纤维化(IPF)和结缔组织疾病相关性间质性肺病(CTD-ILD)患者血浆和外周血单个核细胞(PBMC)中CFL-1的表达显著升高(P<0.05).IPF组(4.2550±0.3483%)和CTD-ILD组(4.7100±0.4811%)外周血纤维细胞百分比均高于对照组(1.6340±0.2549%)(均P<0.05)。体外，转染siRNA-CFL-1的PBMCs显示CFL-1表达较低，纤维细胞百分比低于对照组（P<0.05）。用Lv-CFL-1转染以增加CFL-1表达的PBMC显示出比对照更高的纤维细胞百分比(P<0.05)。在博来霉素诱导的肺纤维化小鼠中，CFL-1的相对表达增加，纤维细胞百分比高于生理盐水组(P<0.05)。在博来霉素诱导的小鼠中，Lv-CFL-1的干扰降低了CFL-1的表达，纤维细胞百分比降低，肺组织纤维化较少(P<0.05)。CFL-1的过表达与肺纤维化发生有关。CFL-1可以促进单核细胞向外周血单个核细胞分化，促进肺纤维化。
