Systemic sclerosis biomarkers detection in the secretome of TGFβ1-activated primary human lung fibroblasts.

Systemic sclerosis biomarkers detection in the secretome of TGFβ1-activated primary human lung fibroblasts.
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TGFβ1 激活的原代人肺成纤维细胞分泌组中系统性硬化症生物标志物的检测。

DOI:
10.1016/j.jprot.2021.104243
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发表时间:
2021-06-30
影响因子:
3.3
通讯作者:
Feghali-Bostwick CA
Feghali-Bostwick CA
中科院分区:
生物学2区
文献类型:
--
作者:
Kendall RT;Renaud L;Baatz JE;Malaab M;Nguyen XX;Feghali-Bostwick CA

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转化生长因子β1是一种促纤维化介质,可导致广泛的病理过程,包括系统性硬化症相关性肺纤维化(SSc-PF)。然而,转化生长因子β-1刺激的原代人正常肺成纤维细胞的分泌体还没有得到很好的描述。应用荧光二维凝胶电泳法(2D-PAGE)和差示凝胶电泳法(DGE)结合质谱法,鉴定了转化生长因子β-1激活的NL成纤维细胞条件培养液中的37个差异分泌蛋白质,并用串法构建了转化生长因子β-1分泌组的蛋白质-蛋白质结合网络。功能丰富表明,PF的几个生物学过程和途径特性得到了丰富。此外,通过将NL成纤维细胞的转化生长因子β-1分泌体与SSc患者生物液中的蛋白质组生物标志物进行比较,我们鉴定了11个重叠的蛋白质。综上所述,我们的数据验证了转化生长因子β1诱导的NL成纤维细胞分泌体是反映SSc生物标志物的有效体外模型,并确定了SSc-PF的潜在治疗靶点。
TGFβ1 is a profibrotic mediator that contributes to a broad spectrum of pathologies, including systemic sclerosis-associated pulmonary fibrosis (SSc-PF). However, the secretome of TGFβ1-stimulated primary human normal lung (NL) fibroblasts has not been well characterized. Using fluorescent 2-dimensional gel electrophoresis (2D-PAGE) and differential gel electrophoresis (DIGE) followed by Mass Spectrometry, we identified 37 differentially secreted proteins in the conditioned media of TGFβ1-activated NL fibroblasts and generated a protein-protein association network of the TGFβ1 secretome using STRING. Functional enrichment revealed that several biological processes and pathways characteristics of PF were enriched. Additionally, by comparing the TGFβ1 secretome of NL fibroblasts to proteomic biomarkers from biological fluids of SSc patients, we identified 11 overlapping proteins. Together our data validate the TGFβ1-induced secretome of NL fibroblasts as a valid in vitro model that reflects SSc biomarkers and identify potential therapeutic targets for SSc-PF.
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