Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism
Background/Aims: Pokeweed antiviral protein (PAP) has been reported to downregulate Wnt/Jnk pathway and attenuate liver fibrosis. This study was designed to intensively explore the mechanism of anti-fibrosis effect of PAP. Materials and Methods: Hepatic stellate cell (HSC) activation was induced by...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2018-01-01
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| Series: | The Saudi Journal of Gastroenterology |
| Subjects: | |
| Online Access: | http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2018;volume=24;issue=3;spage=157;epage=164;aulast=Zhang |
| _version_ | 1818493249714651136 |
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| author | Yonghong Zhang Xiaolan Yu Zheng Wang Ming Yin Zonghao Zhao Yi Li Wenting Li |
| author_facet | Yonghong Zhang Xiaolan Yu Zheng Wang Ming Yin Zonghao Zhao Yi Li Wenting Li |
| author_sort | Yonghong Zhang |
| collection | DOAJ |
| description | Background/Aims: Pokeweed antiviral protein (PAP) has been reported to downregulate Wnt/Jnk pathway and attenuate liver fibrosis. This study was designed to intensively explore the mechanism of anti-fibrosis effect of PAP.
Materials and Methods: Hepatic stellate cell (HSC) activation was induced by high concentration of glucose. Cell viability was detected at different time points after PAP treatment. Meanwhile, hepatic fibrosis models in mice were induced by CCl4 injection. In the end, liver pathology was observed and contents of alanine transaminase, aspartate transaminase, lactic dehydrogenase, hyaluronic acid (HA), and laminin (LN) in serum together with hydroxyproline (Hyp) in liver were measured. The mRNA and protein expressions of HK2, PFKP, PCK1, and FBP1 as well as Jnk expression in HSC-T6 cells and liver tissue were detected by qPCR and western-blot, respectively.
Results: Compared with high glucose, PAP reduced viability and expressions of HK2, PFKP, α-SMA, and Col1A1, where as enhanced the expressions of PCK1 and FBP1 in HSC-T6 cells (P < 0.05) respectively. PAP attenuated liver pathology, improved liver function, and reduced collagen deposition in liver tissue compared with the model group (P < 0.05) respectively. Moreover, PAP reduced expressions of HK2, PFKP, α-SMA, and Col1A1 where as increased the expression of PCK1 and FBP1 in the liver of mice compared with the model group (P < 0.05) respectively. Most importantly, PAP reduced the phosphorylation of Jnk both in cells and liver tissue compared with the model group (P < 0.05) respectively.
Conclusions: Our results demonstrated that PAP attenuated liver fibrosis by regulating Wnt/Jnk-mediated glucose metabolism. It provided us a new target for the treatment of liver fibrosis. |
| first_indexed | 2024-12-10T17:52:21Z |
| format | Article |
| id | doaj.art-906443dc279d48e2a6c7cb36ad5f5be7 |
| institution | Directory Open Access Journal |
| issn | 1319-3767 1998-4049 |
| language | English |
| last_indexed | 2024-12-10T17:52:21Z |
| publishDate | 2018-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | The Saudi Journal of Gastroenterology |
| spelling | doaj.art-906443dc279d48e2a6c7cb36ad5f5be72022-12-22T01:39:02ZengWolters Kluwer Medknow PublicationsThe Saudi Journal of Gastroenterology1319-37671998-40492018-01-0124315716410.4103/sjg.SJG_470_17Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolismYonghong ZhangXiaolan YuZheng WangMing YinZonghao ZhaoYi LiWenting LiBackground/Aims: Pokeweed antiviral protein (PAP) has been reported to downregulate Wnt/Jnk pathway and attenuate liver fibrosis. This study was designed to intensively explore the mechanism of anti-fibrosis effect of PAP. Materials and Methods: Hepatic stellate cell (HSC) activation was induced by high concentration of glucose. Cell viability was detected at different time points after PAP treatment. Meanwhile, hepatic fibrosis models in mice were induced by CCl4 injection. In the end, liver pathology was observed and contents of alanine transaminase, aspartate transaminase, lactic dehydrogenase, hyaluronic acid (HA), and laminin (LN) in serum together with hydroxyproline (Hyp) in liver were measured. The mRNA and protein expressions of HK2, PFKP, PCK1, and FBP1 as well as Jnk expression in HSC-T6 cells and liver tissue were detected by qPCR and western-blot, respectively. Results: Compared with high glucose, PAP reduced viability and expressions of HK2, PFKP, α-SMA, and Col1A1, where as enhanced the expressions of PCK1 and FBP1 in HSC-T6 cells (P < 0.05) respectively. PAP attenuated liver pathology, improved liver function, and reduced collagen deposition in liver tissue compared with the model group (P < 0.05) respectively. Moreover, PAP reduced expressions of HK2, PFKP, α-SMA, and Col1A1 where as increased the expression of PCK1 and FBP1 in the liver of mice compared with the model group (P < 0.05) respectively. Most importantly, PAP reduced the phosphorylation of Jnk both in cells and liver tissue compared with the model group (P < 0.05) respectively. Conclusions: Our results demonstrated that PAP attenuated liver fibrosis by regulating Wnt/Jnk-mediated glucose metabolism. It provided us a new target for the treatment of liver fibrosis.http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2018;volume=24;issue=3;spage=157;epage=164;aulast=ZhangGlucose metabolismliver fibrosisPAPWnt/Jnk |
| spellingShingle | Yonghong Zhang Xiaolan Yu Zheng Wang Ming Yin Zonghao Zhao Yi Li Wenting Li Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism The Saudi Journal of Gastroenterology Glucose metabolism liver fibrosis PAP Wnt/Jnk |
| title | Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism |
| title_full | Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism |
| title_fullStr | Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism |
| title_full_unstemmed | Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism |
| title_short | Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism |
| title_sort | pokeweed antiviral protein attenuates liver fibrosis in mice through regulating wnt jnk mediated glucose metabolism |
| topic | Glucose metabolism liver fibrosis PAP Wnt/Jnk |
| url | http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2018;volume=24;issue=3;spage=157;epage=164;aulast=Zhang |
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