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Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis 期刊论文

编号：

fe0238ee-d6c5-45a5-a2ff-0284f0f8886a
作者：

Yang, Yoon Mee#^[1,2]Noureddin, Mazen#^[1,3]Liu, Cheng(刘成)^[4]Ohashi, Koichiro^[1];Kim, So Yeon^[1];Ramnath, Divya^[5,6];Powell, Elizabeth E.^[7,8];Sweet, Matthew J.^[5,6];Roh, Yoon Seok^[1,9];Hsin, IFang^[1];Deng, Nan^[10];Liu, Zhenqiu^[10];Liang, Jiurong^[1,11,12];Mena, Edward^[13];Shouhed, Daniel^[14];Schwabe, Robert F.^[15];Jiang, Dianhua^[1,11,12];Lu, Shelly C.^[1];Noble, Paul W.^[1,11];Seki, Ekihiro*^[1,12]
语种：

英文
期刊：

SCIENCE TRANSLATIONAL MEDICINE ISSN：1946-6234 2019 年 11 卷 496 期 ; JUN 12
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摘要：

Hyaluronan (HA), a major extracellular matrix glycosaminoglycan, is a biomarker for cirrhosis. However, little is known about the regulatory and downstream mechanisms of HA overproduction in liver fibrosis. Hepatic HA and HA synthase 2 (HAS2) expression was elevated in both human and murine liver fibrosis. HA production and liver fibrosis were reduced in mice lacking HAS2 in hepatic stellate cells (HSCs), whereas mice overexpressing HAS2 had exacerbated liver fibrosis. HAS2 was transcriptionally up-regulated by transforming growth factor-beta through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4 (TLR4), and newly identified downstream effector Notch1. Inhibition of HA synthesis by 4-methylumbelliferone reduced HSC activation and liver fibrosis in mice. Our study provides evidence that HAS2 actively synthesizes HA in HSCs and that it promotes HSC activation and liver fibrosis through Notch1. Targeted HA inhibition may have potential to be an effective therapy for liver fibrosis.
推荐引用方式
GB/T 7714：

Yang Yoon Mee,Noureddin Mazen,Liu Cheng, et al. Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis [J].SCIENCE TRANSLATIONAL MEDICINE,2019,11(496).
APA：

Yang Yoon Mee,Noureddin Mazen,Liu Cheng,Ohashi Koichiro,&Seki Ekihiro.(2019).Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis .SCIENCE TRANSLATIONAL MEDICINE,11(496).
MLA：

Yang Yoon Mee, et al. "Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis" .SCIENCE TRANSLATIONAL MEDICINE 11,496(2019).
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