Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx
Background<p>Liver fibrosis, driven by excessive extracellular matrix (ECM) deposition and activation of hepatic stellate cells (HSCs), still lacks effective therapies, partly due to the absence of human-relevant models. Lycii Radicis Cortex (LRC), a traditional Chinese medicine, exhibits repo...
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2025
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| _version_ | 1849927630966489088 |
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| author | Junming Xu (1716112) |
| author2 | Xiaopu Sang (8502954) Yongfei He (21372968) Jie Ke (2005411) Jiasen Xu (729951) Tanbin Liu (4849807) Jicai Wang (21372977) Hang Zhai (1540051) Xiaoni Chen (8502957) Xianjie Shi (3567419) Fenfang Wu (3157299) |
| author2_role | author author author author author author author author author author |
| author_facet | Junming Xu (1716112) Xiaopu Sang (8502954) Yongfei He (21372968) Jie Ke (2005411) Jiasen Xu (729951) Tanbin Liu (4849807) Jicai Wang (21372977) Hang Zhai (1540051) Xiaoni Chen (8502957) Xianjie Shi (3567419) Fenfang Wu (3157299) |
| author_role | author |
| dc.creator.none.fl_str_mv | Junming Xu (1716112) Xiaopu Sang (8502954) Yongfei He (21372968) Jie Ke (2005411) Jiasen Xu (729951) Tanbin Liu (4849807) Jicai Wang (21372977) Hang Zhai (1540051) Xiaoni Chen (8502957) Xianjie Shi (3567419) Fenfang Wu (3157299) |
| dc.date.none.fl_str_mv | 2025-11-25T14:14:47Z |
| dc.identifier.none.fl_str_mv | 10.3389/fphar.2025.1730255.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Supplementary_file_2_Lycii_radicis_cortex_alleviates_fibrosis_in_hiPSC-derived_multilineage_hepatic_organoids_via_the_cAMP-PKA_pathway_docx/30710582 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Pharmacology natural products IPSCs (induced pluripotent stem cells) organoid liver fibrosis lycii radicis cortex cAMP–PKA–CREB pathway |
| dc.title.none.fl_str_mv | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Background<p>Liver fibrosis, driven by excessive extracellular matrix (ECM) deposition and activation of hepatic stellate cells (HSCs), still lacks effective therapies, partly due to the absence of human-relevant models. Lycii Radicis Cortex (LRC), a traditional Chinese medicine, exhibits reported anti-inflammatory and antioxidant activities, yet its anti-fibrotic potential has not been validated in human organoid-based systems.</p>Methods<p>We established hiPSC-derived multilineage hepatobiliary organoids (mHBOs) containing mesoderm-derived HSCs and implemented a TGF-β–induced fibrosis model within this platform. Using mHBOs alongside a CCl4-injury mouse model, we assessed the anti-fibrotic activity of LRC, and investigated underlying mechanisms.</p>Results<p>LRC significantly attenuated fibrosis in mHBOs and in CCl<sub>4</sub>-injured mice, reducing ECM accumulation and HSC activation. In mHBOs, LRC activated the cAMP–PKA–CREB pathway, thereby suppressing HSC activation and reducing parenchymal apoptosis; these effects were reversed by PKA inhibition.</p>Conclusion<p>LRC exhibits potent anti-fibrotic activity in a physiologically relevant human organoid model, providing mechanistic insight into HSC regulation and supporting its potential as a candidate therapy for chronic liver disease. Furthermore, this study introduces a translational platform integrating animal models and hiPSC-derived organoids to facilitate anti-fibrotic drug discovery and evaluation.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_ddd1714e57bd0960944d472afd218697 |
| identifier_str_mv | 10.3389/fphar.2025.1730255.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30710582 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docxJunming Xu (1716112)Xiaopu Sang (8502954)Yongfei He (21372968)Jie Ke (2005411)Jiasen Xu (729951)Tanbin Liu (4849807)Jicai Wang (21372977)Hang Zhai (1540051)Xiaoni Chen (8502957)Xianjie Shi (3567419)Fenfang Wu (3157299)Pharmacologynatural productsIPSCs (induced pluripotent stem cells)organoidliver fibrosislycii radicis cortexcAMP–PKA–CREB pathwayBackground<p>Liver fibrosis, driven by excessive extracellular matrix (ECM) deposition and activation of hepatic stellate cells (HSCs), still lacks effective therapies, partly due to the absence of human-relevant models. Lycii Radicis Cortex (LRC), a traditional Chinese medicine, exhibits reported anti-inflammatory and antioxidant activities, yet its anti-fibrotic potential has not been validated in human organoid-based systems.</p>Methods<p>We established hiPSC-derived multilineage hepatobiliary organoids (mHBOs) containing mesoderm-derived HSCs and implemented a TGF-β–induced fibrosis model within this platform. Using mHBOs alongside a CCl4-injury mouse model, we assessed the anti-fibrotic activity of LRC, and investigated underlying mechanisms.</p>Results<p>LRC significantly attenuated fibrosis in mHBOs and in CCl<sub>4</sub>-injured mice, reducing ECM accumulation and HSC activation. In mHBOs, LRC activated the cAMP–PKA–CREB pathway, thereby suppressing HSC activation and reducing parenchymal apoptosis; these effects were reversed by PKA inhibition.</p>Conclusion<p>LRC exhibits potent anti-fibrotic activity in a physiologically relevant human organoid model, providing mechanistic insight into HSC regulation and supporting its potential as a candidate therapy for chronic liver disease. Furthermore, this study introduces a translational platform integrating animal models and hiPSC-derived organoids to facilitate anti-fibrotic drug discovery and evaluation.</p>2025-11-25T14:14:47ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fphar.2025.1730255.s002https://figshare.com/articles/dataset/Supplementary_file_2_Lycii_radicis_cortex_alleviates_fibrosis_in_hiPSC-derived_multilineage_hepatic_organoids_via_the_cAMP-PKA_pathway_docx/30710582CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307105822025-11-25T14:14:47Z |
| spellingShingle | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx Junming Xu (1716112) Pharmacology natural products IPSCs (induced pluripotent stem cells) organoid liver fibrosis lycii radicis cortex cAMP–PKA–CREB pathway |
| status_str | publishedVersion |
| title | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| title_full | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| title_fullStr | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| title_full_unstemmed | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| title_short | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| title_sort | Supplementary file 2_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.docx |
| topic | Pharmacology natural products IPSCs (induced pluripotent stem cells) organoid liver fibrosis lycii radicis cortex cAMP–PKA–CREB pathway |