Supplementary file 1_Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway.zip
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...
Gorde:
| Egile nagusia: | |
|---|---|
| Beste egile batzuk: | , , , , , , , , , |
| Argitaratua: |
2025
|
| Gaiak: | |
| Etiketak: |
Etiketa erantsi
Etiketarik gabe, Izan zaitez lehena erregistro honi etiketa jartzen!
|
| Gaia: | 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> |
|---|