Lipid content was quantified by HPLC and mass spectroscopy. Primary HSCs were treated with nuclear

receptor ligands, transfected with siRNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ-/- HSCs have increased cholesterol and retinyl esters (CEs & REs). The retinoid increase drives intrinsic retinoic acid receptor (RAR) signaling and activation occurs more rapidly in Lxrαβ-/- HSCs. We identify Rab18 STI571 mw as a novel retinoic acid responsive, lipid droplet associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 GTPase activity and isoprenylation are required for stellate cell lipid droplet loss and induction of activation markers. These lambrolizumab phenomena are accelerated in the Lxrαβ-/- HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards lipid droplet loss in culture and blocks activation, just like the functional mutants. Rab18 is also

induced with acute liver injury in vivo. Conclusion: Retinoid and cholesterol metabolism are linked in stellate cells by the LD associated protein, Rab18. Retinoid overload helps explain the pro-fibrotic phenotype of Lxrαβ-/- mice and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild-type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. This article is protected by copyright. All rights reserved. “
“We read with great interest the article by Iavarone et al.,1 who studied the role of tumor grading in the diagnosis of hepatocellular carcinoma (HCC) detected during surveillance by dynamic contrast imaging techniques in patients with compensated cirrhosis. The authors showed that the tumor grade and size influence the accuracy of imaging techniques in HCC diagnosis; in fact, accuracy was greater for poorly differentiated (high-grade)

nodules > 2 cm versus more differentiated (low-grade) nodules ≤ 2 cm. These observations indirectly confirm the correlation between HCC grade and vascularization: high-grade HCC is better detected by imaging.2, 3 We appreciate the attempt of Iavarone et al.1 to find a correlation between diagnostic imaging techniques and HCC grading because selleck kinase inhibitor the latter greatly influences HCC outcomes and is a strong predictor of recurrence after surgery. However, we believe that the only way to obtain preoperative histological information is needle core biopsy (NCB). We recently evaluated the overall accuracy of preoperative NCB in assessing tumor grading in patients with cirrhosis undergoing liver resection for a single HCC.4 We found that preoperative NCB is a safe procedure (no serious adverse events were observed) and an accurate tool for assessing the tumor grade, particularly for small HCCs.