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Pepstatin Pr show anti-fibrosis effect related to YAP-TGFβ-Smad pathway
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Wei-xiao NIU, Ming-hua CHEN, Na ZHANG, Mao-xu GE, Yun-yang BAO, Shu-yi SI, Rong-guang SHAO, Hong-wei HE*
Acta Pharmaceutica Sinica | 2019, 54(1) : 89 - 94
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Acta Pharmaceutica Sinica | 2019, 54(1): 89-94
Original Articles
Pepstatin Pr show anti-fibrosis effect related to YAP-TGFβ-Smad pathway
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Wei-xiao NIU, Ming-hua CHEN, Na ZHANG, Mao-xu GE, Yun-yang BAO, Shu-yi SI, Rong-guang SHAO, Hong-wei HE*
Affiliations
  • Inititute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2019-01-12 doi: 10.16438/j.0513-4870.2018-0705
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Liver fibrosis is a tissue repair compensatory response to liver injury caused by various chronic factors, ultimately leading to liver cirrhosis, liver failure and even hepatocellular carcinoma. Abnormal activation of hepatic stellate cells is the cellular basis of liver fibrosis development. Pepstatin Pr, the derivative of pepstatin A, was isolated from Streptomyces sp. CPCC 202950. Our purpose was to investigate the anti-fibrotic activity of pepstatin Pr and explore its molecular mechanism. Hepatic stellate cell LX-2 was stimulated by TGFβ1 and sub-sequently treated with pepstatin Pr. Its cytotoxicity was detected by sulforhodamine B (SRB) assay. The expression of COL1A1, α-SMA and cathepsin D, signaling proteins TGFβ, Smad and YAP/TAZ were detected by Western blot or real-time PCR. The results showed that pepstatin Pr was not cytotoxic to LX-2 cells. And pepstatin Pr significantly reduced the mRNA and protein expression of COL1A1 and α-SMA, which are important liver fibrosis markers. Pepstatin Pr also repressed the protein expression level of cathepsin D, TGFβ1, YAP/TAZ, the phospholation level of Smad2, and YAP nuclear translocation. In conclusion, pepstatin Pr exhibits anti-fibrotic effects in TGFβ1-stimulaed LX-2 cells by mediating YAP-TGFβ-Smad pathway.

liver fibrosis  /  cathepsin D  /  TGFβ-Smad  /  YAP/TAZ
Wei-xiao NIU, Ming-hua CHEN, Na ZHANG, Mao-xu GE, Yun-yang BAO, Shu-yi SI, Rong-guang SHAO, Hong-wei HE. Pepstatin Pr show anti-fibrosis effect related to YAP-TGFβ-Smad pathway[J]. Acta Pharmaceutica Sinica, 2019 , 54 (1) : 89 -94 . DOI: 10.16438/j.0513-4870.2018-0705
Year 2019 volume 54 Issue 1
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doi: 10.16438/j.0513-4870.2018-0705
  • Receive Date:2018-08-03
  • Online Date:2026-01-26
  • Published:2019-01-12
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  • Received:2018-08-03
  • Revised:2018-10-11
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    Inititute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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