PT  - JOURNAL ARTICLE
AU  - Mao Na
AU  - Xu Hong
AU  - Jin Fuyu
AU  - Xu Dingjie
AU  - Dominic Sales
AU  - Zhang Hui
AU  - Wei Zhongqiu
AU  - Li Shifeng
AU  - Gao Xuemin
AU  - Cai Wenchen
AU  - Li Dan
AU  - Zhang Guizhen
AU  - Zhang Bonan
AU  - Zhang Lijuan
AU  - Li Shumin
AU  - Zhu Ying
AU  - Wang Jin
AU  - Rui Mingwang
AU  - Ross Summer
AU  - Yang Fang
TI  - Proteomic Profile of TGF-β1 treated Lung Fibroblasts identifies Novel Markers of Activated Fibroblasts in the Silica Exposed Rat Lung
AID  - 10.1101/431825
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 431825
4099  - http://biorxiv.org/content/early/2018/10/01/431825.short
4100  - http://biorxiv.org/content/early/2018/10/01/431825.full
AB  - We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-β1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-β1 treatment and 196 proteins were expressed at ≥ 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-β1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-β1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-β1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.Highlights We identified 196 proteins differentially expressed between control and TGF-β1 treated fibroblastsby LC-MS/MS.Several proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2Knockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.