Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy
文献类型：期刊论文
| 作者 | Wu, Shouyan1,3,4; Cao, Yuhan3,4; Lu, Henglei4; Qi, Xinming4 ; Sun, Jianhua4; Ye, Yang3,4; Gong, Likun1,2,3,4
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| 刊名 | BIOMEDICINE & PHARMACOTHERAPY
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| 出版日期 | 2022-09-01 |
| 卷号 | 153页码:12 |
| 关键词 | Primary sclerosing cholangitis (PSC) Peribiliary gland niche Ductular reaction Fibrosis Therapeutic strategy 18?-glycyrrhetinic acid (GA) |
| ISSN号 | 0753-3322 |
| DOI | 10.1016/j.biopha.2022.113512 |
| 通讯作者 | Wu, Shouyan(wushy1@163.com) ; Ye, Yang(yye@simm.ac.cn) ; Gong, Likun(lkgong@cdser.simm.ac.cn) |
| 英文摘要 | Primary sclerosing cholangitis (PSC) is a rare but progressive and fatal autoimmune disease without clear pathogenesis and effective therapies. Peribiliary macrophage recruitment and peribiliary gland (PBG) proliferation and expansion have been associated with various cholangiopathies. This study aimed to evaluate the involvement of the PBG niche and macrophages in PSC progression, potential treatment strategies, and the underlying mechanism in acute and chronic experimental PSC. First, the upregulation of chemokines and fibrosis in PSC patients was confirmed via RNA-seq analysis. In vivo data illustrated that inflammation and fibrosis are the main characteristics, and recession of these can effectively interfere with PSC. Histopathological staining and RTPCR revealed that more significant ductular reaction (DR) and PBG proliferation in the chronic PSC model, in which fibrosis mainly accumulated in the peribiliary area. In vitro, a transwell migration experiment showed that MCP-1 secreted by cholangiocytes in PBG niche, which recruited monocyte-derived macrophages (MoMFs) to the peribiliary area and promoted inflammation and fibrosis. Then, the luciferase assay and EMSA showed that POU6F1 could activate MCP-1 transcription. Furthermore, 18 beta-Glycyrrhetinic acid (GA) reduced macrophages and fibrosis accumulated in the peribiliary, space and reduced PBG proliferation to benefit acute and chronic PSC models. Collectively, our results indicated that POU6F1 transcriptionally activates MCP-1, promoting the recruitment and infiltration of MoMFs and fibrosis into the PBG niche in PSC mouse models, and GA effectively suppressed the above phenotypes. These findings provide potential targets and a theoretical basis for the clinical treatment of PSC. |
| WOS关键词 | BILIARY TREE ; STEM-CELLS ; PHOSPHORYLATION ; PROLIFERATION ; PATHOGENESIS ; ACTIVATION ; RATS |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000838929500001 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302293]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wu, Shouyan; Ye, Yang; Gong, Likun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, 501 Hai Ke Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Shouyan,Cao, Yuhan,Lu, Henglei,et al. Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy[J]. BIOMEDICINE & PHARMACOTHERAPY,2022,153:12. |
| APA | Wu, Shouyan.,Cao, Yuhan.,Lu, Henglei.,Qi, Xinming.,Sun, Jianhua.,...&Gong, Likun.(2022).Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy.BIOMEDICINE & PHARMACOTHERAPY,153,12. |
| MLA | Wu, Shouyan,et al."Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy".BIOMEDICINE & PHARMACOTHERAPY 153(2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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