Animal and organoid models to elucidate the anti-fibrotic effect of steroid on biliary atresia
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In brief
In brief
This study uses rhesus rotavirus-induced mouse models and liver organoids to demonstrate that corticosteroid treatment significantly reduces liver fibrosis in biliary atresia. Steroid-treated mice showed improved weight gain, lower bilirubin levels, and markedly reduced fibrosis compared to controls, with RNA sequencing revealing over 6000 differentially expressed genes between treatment groups.
- Steroid treatment significantly reduced liver fibrosis in RRV-induced biliary atresia mouse models (1/12 vs 12/12 developed fibrosis).
- Steroid-treated BA mice showed improved weight gain and significantly lower serum bilirubin and liver enzyme levels compared to controls.
- Liver organoid models demonstrated distinct morphological differences and 6359 differentially expressed genes with steroid treatment.
- Animal and organoid models provide complementary evidence that steroids may have anti-fibrotic therapeutic potential in biliary atresia.
- Post-Kasai steroid therapy warrants further investigation based on these preclinical findings showing fibrosis mitigation.
Written by the GCMD Library team from the article.
Abstract
Purpose
We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism.
Methods
BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34. On day 34, their serum samples were collected for hormonal markers. Necrosis, fibrosis and CK 19 expression in the liver were evaluated. Liver organoids were developed and their morphology as well as bulk RNA sequencing data were analyzed.
Results
Twenty-four mice developed BA features after RRV injection and were equally divided into steroid and PBS groups. On day 34, the weight gain of steroid group increased significantly than PBS group (p < 0.0001). All mice in the PBS group developed liver fibrosis but only one mouse in the steroid group did. Serum bilirubin and liver parenchymal enzymes were significantly lower in steroid group. The morphology of liver organoids were different between the two groups. A total of 6359 differentially expressed genes were found between steroid group and PBS group.
Conclusion
Based on our findings obtained from RRV-induced BA animal and organoid models, steroid has the potential to mitigate liver fibrosis in BA.