isolation-culture-primary-cholangiocytes-from-mice-with-polycystic

Isolation and Culture of Primary Cholangiocytes from Mice with Polycystic Liver Disease Using a Two-step Digestion Method

In this protocol, we optimized a two-step digestion method to isolate high-purity and high-viability primary cholangiocytes from wild-type mice and mice ...

multi-omics-techniques-for-profiling-chromatin-state-transitions-low

Multi-omics Techniques for Profiling Chromatin State Transitions in Low-input Primary Mouse Cholangiocytes

Polycystic liver disease (PLD) is a hereditary disorder characterized by the formation of fluid-filled cysts derived from cholangiocytes, leading to ...

Tianjin Medical University

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.

White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism.

Cholangiocytes transit from quiescence to hyperproliferation during cystogenesis in polycystic liver disease (PLD), the severity of which displays prominent sex differences. Epigenetic regulation plays important roles in cell state transition. We aimed to investigate the sex-specific epigenetic basis of hepatic cystogenesis and to develop therapeutic strategies targeting epigenetic modifications for PLD treatment.

Multi-omics profiling of cholangiocytes reveals sex-specific chromatin state dynamics during hepatic cystogenesis in polycystic liver disease.

Cellular prion protein (PrP), known for its pathological isoform in prion diseases such as Creutzfeldt-Jakob disease, is primarily expressed in the nervous system but has also been detected in the blood and urine of individuals with renal dysfunction. However, the role of PrP in the development of renal disease is unexplored. Here, we showed that PrP was up-regulated in fibrotic renal lesions in biopsies from patients with chronic kidney disease (CKD), predominantly in proximal tubular epithelial cells (PTECs). Furthermore, renal expression of PrP was positively correlated with the severity of renal failure and the decline in estimated glomerular filtration rate in patients with CKD. In mice, tubular-specific deletion of PrP mitigated renal fibrosis induced by unilateral ureteral obstruction (UUO) or unilateral ischemia-reperfusion injury (UIRI). Mechanistically, PrP was up-regulated by transforming growth factor-β1-suppressor of mothers against decapentaplegic 3 signaling. PrP activated TANK binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) signaling through its capacity for liquid-liquid phase separation, which promoted a profibrotic response in PTECs and fibroblasts. Treating mice with amlexanox, a US Food and Drug Administration-approved inhibitor of TBK1, either before the onset of renal fibrosis (in UUO and UIRI models) or after its establishment (in adenine- and aristolochic acid-induced CKD models), mitigated worsening of renal fibrosis and renal function. Collectively, our findings uncovered a mechanism involving phase separation of PrP underlying renal fibrosis and support further study of the PrP-TBK1-IRF3 axis as a potential therapeutic target for CKD.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2025

Article	Year
White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism. Gene\| PubMed ID: 35569768	2022
Multi-omics profiling of cholangiocytes reveals sex-specific chromatin state dynamics during hepatic cystogenesis in polycystic liver disease. Journal of hepatology\| PubMed ID: 36681161	2023
Condensation of cellular prion protein promotes renal fibrosis through the TBK1-IRF3 signaling axis. Science translational medicine\| PubMed ID: 40238918	2025

Jiayuan Chen

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