Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/99325
標題: Non-Canonical Regulation of Type I Collagen through Promoter Binding of SOX2 and Its Contribution to Ameliorating Pulmonary Fibrosis by Butylidenephthalide
作者: Chuang, Hong-Meng
Ho, Li-Ing
Huang, Mao-Hsuan
Huang, Kun-Lun
Chiou, Tzyy-Wen
Lin, Shinn-Zong
Su, Hong-Lin
蘇鴻麟
Harn, Horng-Jyh
關鍵字: SOX2;bleomycin;butylidenephthalide;pulmonary fibrosis;type I collagen;Animals;Cell Line;Collagen Type I;Fibroblasts;Humans;Male;Mice;Mice, Inbred C57BL;Phthalic Anhydrides;Promoter Regions, Genetic;Pulmonary Fibrosis;SOXB1 Transcription Factors
Project: International journal of molecular sciences, Volume 19, Issue 10
摘要: 
Pulmonary fibrosis is a fatal respiratory disease that gradually leads to dyspnea, mainly accompanied by excessive collagen production in the fibroblast and myofibroblast through mechanisms such as abnormal alveolar epithelial cells remodeling and stimulation of the extracellular matrix (ECM). Our results show that a small molecule, butylidenephthalide (BP), reduces type I collagen (COL1) expression in Transforming Growth Factor beta (TGF-β)-induced lung fibroblast without altering downstream pathways of TGF-β, such as Smad phosphorylation. Treatment of BP also reduces the expression of transcription factor Sex Determining Region Y-box 2 (SOX2), and the ectopic expression of SOX2 overcomes the inhibitory actions of BP on COL1 expression. We also found that serial deletion of the SOX2 binding site on 3'COL1 promoter results in a marked reduction in luciferase activity. Moreover, chromatin immunoprecipitation, which was found on the SOX2 binding site of the COL1 promoter, decreases in BP-treated cells. In an in vivo study using a bleomycin-induced pulmonary fibrosis C57BL/6 mice model, mice treated with BP displayed reduced lung fibrosis and collagen deposition, recovering in their pulmonary ventilation function. The reduction of SOX2 expression in BP-treated lung tissues is consistent with our findings in the fibroblast. This is the first report that reveals a non-canonical regulation of COL1 promoter via SOX2 binding, and contributes to the amelioration of pulmonary fibrosis by BP treatment.
URI: http://hdl.handle.net/11455/99325
DOI: 10.3390/ijms19103024
Appears in Collections:生命科學系所

Files in This Item:
File Description SizeFormat Existing users please Login
335.pdf6.87 MBAdobe PDFThis file is only available in the university internal network    Request a copy
Show full item record
 

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.