No abstract

No abstract

Due to the inherent limitations of the mouse models, the molecular mechanism of TGFβ signaling involved in the development of intrahepatic bile ducts (IHBDs) has been investigated little. Here, we investigated the role of TGFβ signaling and its regulatory mechanism in IHBDs development. We demonstrate that TGFβ signaling pathway activity is essential for IHBDs development. When blocking TGFβ signaling at E10.5, the number of bile ducts in hilum was reduced more than two fold and number of CK19 positive chlangiocytes in periphery was reduced more than 3.5-fold compared with controls. We also show that alpha-smooth muscle actin (α-SMA)-immunoreactive cells are located in the portal vein mesenchyme (PVM) adjacent to the bile ducts during IHBDs development and identify the α-SMA positive cells expressing the Notch ligand Jagged1 in the periportal area. Importantly, after blocking TGFβ signaling, the expression of Jagged1 was selectively decreased in the PVM but not in biliary epithelial cells (BECs), which is associated with the transformation of portal mesenchyme cells (PMCs) into portal myofibroblasts (PMFs). In addition, Sox9, which is downstream of Notch, is decreased after blocking the TGFβ signaling pathway in the liver. Our findings uncover a novel mechanism of TGFβ signaling in controlling the development of IHBDs may through regulating the Jagged1-Notch-Sox9 signaling axis.

No abstract

Purpose: Coexistence of hepatocellular carcinoma (HCC) and cystic echinococcus (CE) is extremely rare. Echinococcus granulosus may exhibit a protective effect against cancer. Herein, this study aimed to evaluate the possible effects of echinococcal infection on HCC patients. Methods: Three thousand three hundred hepatic CE patients and 815 HCC patients were retrospectively reviewed between January 2010 and December 2018 in Xinjiang, China, and these patients were 1:5 matched according to their sex, age and tumor TMN stage, and only 13 patients coexisted both CE and HCC. Preoperative ultrasonography (US), computed tomography (CT), liver magnetic resonance imaging (MRI) and dot immune-gold filtration assay (DIGFA) were used for preoperative identification and intraoperative specimens from liver resections were pathologically examined for further confirmation. Survival time was analyzed through Cox proportional hazard model analysis. Results: The co-existing incidence rate of two diseases was 0.39%. For these concurrent cases, HCC was all at the advanced stage and CE lesions were inactive. Median survival time for HCC patients was 6 month (1-17). However, it was 8 month (3-90) for the co-existing cases and was much longer than the median survival time of HCC patients (P< 0.05), which was closely associated with tumor size, location, TMN stage and hydatid size, location, classification. Four of the patients underwent surgical intervention and their median survival time was 17 month (3-68). Conclusions: Echinococcus granulosus may elicit a protective effect against the development and progression of HCC, while more basic and clinical researches are needed.

No abstract

No abstract

Hepatic stellate cells (HSCs) play an important microenvironmental role in hepatic progenitor cells (HPCs) differentiation fate. To reveal the specific mechanism of HSCs induced by transforming growth factor β1 (TGF‐β1) signaling in HPCs differentiation process, we used Knockin and knockdown technologies induced by lentivirus to upregulate or downregulate TGF‐β1 level in mouse HSCs (mHSCs) (mHSCs‐TGF‐β1 or mHSCs‐TGF‐βR1sih3). Primary mouse HPCs (mHPCs) were isolated and were cocultured with mHSCs‐TGF‐β1 and mHSCs‐TGF‐βR1sih3 for 7 days. Differentiation of mHPCs was detected by quantitative reverse transcriptase polymerase chain reaction analysis and immunofluorence in vitro. mHPCs‐E14.5 cell lines and differently treated mHSCs were cotransplanted into mice spleens immediately after establishment of acute liver injury model for animal studies. Engraftment and differentiation of transplanted cells as well as liver function recovery were measured at the seventh day via different methods. mHSCs‐TGF‐β1 were transformed into myofibroblasts and highly expressed Jagged1, but that expression was reduced after blockage of TGF‐β1 signaling. mHPCs highly expressed downstream markers of Jagged1/Notch signaling and cholangiocyte markers (CK19, SOX9, and Hes1) after coculture with mHSCs‐TGF‐β1 in vitro. In contrast, mature hepatocyte marker (ALB) was upregulated in mHPCs in coculture conditions with mHSCs‐TGF‐βR1sih3. At the seventh day of cell transplantation assay, mHPCs‐E 14.5 engrafted and differentiated into cholangiocytes after cotransplanting with TGF‐β1‐knockin mHSCs, but the cells had a tendency to differentiate into hepatocytes when transplanted with TGF‐βR1‐knockdown mHSCs, which corresponded to in vitro studies. HSCs play an important role in regulating HPCs differentiation into cholangiocytes via the TGF‐β1/Jagged1 signaling axis. However, HPCs have a tendency to differentiate into hepatocytes after blockage of TGF‐β1 signaling in HSCs.