Transcriptomic analysis of active form of Srebf1-overexpressed fibroblasts in bleomycin-induced lung fibrosis

Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although lung fibroblasts play central roles in PF, their key regulatory molecules remain unclear. We performed transcriptome analysis of lung fibroblasts from bleomycin- and silica-treated murine lungs and identified 55 hub transcription factors highly connected to gene modules differentially expressed in PF. To elucidate whether fibroblast-specific intervention against the hub transcription factor Srebf1 modulates pathogenic activation of lung fibroblasts in vivo, we intratracheally-transferred active form of Srebf1-overexpressed fibroblasts into bleomycin-treated lungs and performed global transcriptome analysis. Overall design: Active form of Srebf1-overexpressed fibroblasts and mock-expressed fibroblasts were intratracheally-transferred to B6 mice at day 5 post-administration of 2 mg/kg of bleomycin. Expression of active form of Srebf1 was induced by doxycycline administration at day 7 post-administration of 2 mg/kg of bleomycin. Donor cells were recovered at day 10 post--administration of 2 mg/kg of bleomycin by cell sorting. Global transcriptome of transferred fibroblasts was generated by 3'SAGE-seq using Ion Proton sequencer.

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Shichino S, Ueha S, Hashimoto S, Otsuji M, Abe J, Tsukui T, Deshimaru S, Nakajima T, Kosugi-Kanaya M, Shand FH, Inagaki Y, Shimano H, Matsushima K