Effects of thrombopoietin on TGFβ1-induced myofibroblast transdifferentiation in hu-man lung fibroblasts
10.3969/j.issn.1000-8179.2019.05.123
- VernacularTitle:血小板生成素抑制TGFβ1诱导的肺成纤维细胞向肌成纤维细胞转化的研究*
- Author:
Boyu QIN
1
;
Jinliang WANG
;
Xiaoguang QI
;
Ran TAO
;
Xin ZHOU
;
Tao WU
Author Information
1. 中国人民解放军总医院第一医学中心肿瘤内科(北京市100853
- Keywords:
thrombopoietin;
TGFβ1;
lung cancer;
pulmonary fibroblast;
collagen synthesis
- From:
Chinese Journal of Clinical Oncology
2019;46(5):218-222
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of thrombopoietin (TPO) on proliferation and collagen synthesis in pulmonary fibro-blasts induced by TGFβ1. Methods: Cultured human embryonic lung fibroblasts (HFLs) were treated with recombinant human TGF-β1 to induce myofibroblast differentiation. Different concentrations of recombinant human TPO were applied individually or in combina-tion. Cell proliferation rate was determined using the CCK8 assay. Q-PCR and immunofluorescence assay were employed to examine the mRNA and protein expression of α-smooth muscle actin (αSMA) and type I collagen (COL1)A2. Results: TGFβ1 treatment induced HFL transdifferentiation to myofibroblasts was determined by the expression of αSMA, a myofibroblast-specific marker. Cell prolifera-tion increased during the induction. COL1 gene and protein expression were upregulated by TGFβ1 induction (P<0.05). The TGFβ1-in-duced mRNA and protein expression of αSMA and COL1A2 was decreased by TPO treatment (P<0.05), as determined by reverse tran-scription quantitative polymerase chain reaction and immunofluorescence analysis, respectively. The inhibitory rate showed a dose de-pendent effect within a certain TPO concentration range. The CCK8 assay demonstrated that TPO downregulated the TGFβ1-induced proliferation (P<0.05). Furthermore, the expression of heme oxygenase-1 (HO-1) was downregulated in TGFβ1-induced lung fibro-blasts, and these effects were attenuated by TPO administration (P<0.05). Conclusions: TPO can inhibit the TGFβ1-induced prolifera-tion and differentiation of human lung fibroblasts. These effects may be mediated in part by HO-1-related signaling pathways.
