Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model
Abstract Background The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Biotechnology |
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| Online Access: | https://doi.org/10.1186/s12896-023-00810-9 |
| _version_ | 1797452174211416064 |
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| author | Lu Shi Tiantian Zhao Lei Huang Xiaomin Pan Tianzhen Wu Xin Feng Taoli Chen Jiamin Wu Jianlou Niu |
| author_facet | Lu Shi Tiantian Zhao Lei Huang Xiaomin Pan Tianzhen Wu Xin Feng Taoli Chen Jiamin Wu Jianlou Niu |
| author_sort | Lu Shi |
| collection | DOAJ |
| description | Abstract Background The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. Results We found that, similar to that of FGF19WT, the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models. The therapeutic benefits of FGF19ΔKLB on cholestatic liver damage are attributable, according to the following mechanistic investigation, to the reduction of BA production, liver inflammation, and fibrosis. More importantly, FGF19ΔKLB did not induce any tumorigenesis effects during its prolonged treatment. Conclusions Together, our findings raise hope that FGF19ΔKLB may represent a useful therapeutic strategy for the treatment of intrahepatic cholestasis. |
| first_indexed | 2024-03-09T15:04:01Z |
| format | Article |
| id | doaj.art-752e3deb8380431b907f6acfa6bbc775 |
| institution | Directory Open Access Journal |
| issn | 1472-6750 |
| language | English |
| last_indexed | 2024-03-09T15:04:01Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biotechnology |
| spelling | doaj.art-752e3deb8380431b907f6acfa6bbc7752023-11-26T13:44:00ZengBMCBMC Biotechnology1472-67502023-10-0123111410.1186/s12896-023-00810-9Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice modelLu Shi0Tiantian Zhao1Lei Huang2Xiaomin Pan3Tianzhen Wu4Xin Feng5Taoli Chen6Jiamin Wu7Jianlou Niu8School of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversitySchool of Pharmaceutical Science, Wenzhou Medical UniversityPingyang Affiliated Hospital of Wenzhou Medical UniversityAbstract Background The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. Results We found that, similar to that of FGF19WT, the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models. The therapeutic benefits of FGF19ΔKLB on cholestatic liver damage are attributable, according to the following mechanistic investigation, to the reduction of BA production, liver inflammation, and fibrosis. More importantly, FGF19ΔKLB did not induce any tumorigenesis effects during its prolonged treatment. Conclusions Together, our findings raise hope that FGF19ΔKLB may represent a useful therapeutic strategy for the treatment of intrahepatic cholestasis.https://doi.org/10.1186/s12896-023-00810-9FGF19Hepatocellular carcinomaBile acidsIntrahepatic cholestasisInflammation |
| spellingShingle | Lu Shi Tiantian Zhao Lei Huang Xiaomin Pan Tianzhen Wu Xin Feng Taoli Chen Jiamin Wu Jianlou Niu Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model BMC Biotechnology FGF19 Hepatocellular carcinoma Bile acids Intrahepatic cholestasis Inflammation |
| title | Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model |
| title_full | Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model |
| title_fullStr | Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model |
| title_full_unstemmed | Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model |
| title_short | Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model |
| title_sort | engineered fgf19δklb protects against intrahepatic cholestatic liver injury in anit induced and mdr2 mice model |
| topic | FGF19 Hepatocellular carcinoma Bile acids Intrahepatic cholestasis Inflammation |
| url | https://doi.org/10.1186/s12896-023-00810-9 |
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