Chun-Ying Huang

Epigenetic histone methylation regulates transforming growth factor β-1 expression following bile duct ligation in rats

BackgroundMultiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor β-1 (TGF-β1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-β1 gene expression in rat liver.MethodsTime course of methylated-histone H3 and SET7/9 recruitment were determined by chromatin immunoprecipitation in livers from BDL rats on days 1, 4, 9 and 14. Levels of TGF-β1 and SET7/9 were determined by western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF-β1, serum enzymes and liver collagen content was studied in vivo.ResultsResults showed that BDL increased the expression of the TGF β-1. Increased levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased levels of repressive marks (H3K9me2 and H3K9me3) in TGF-β1 promoter accompanied the changes in expression of the TGF β-1. BDL also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter. SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-β1 gene expression, serum enzymes and liver collagen content.ConclusionsTaken together, these results show the functional role of epigenetic chromatin histone H3Kme in BDL-induced TGF-β1 expression. Pharmacologic and other therapies that reverse these modifications could have potential hepatoprotective effects for BDL-induced cirrhosis.

Nonsurgical management of delayed splenic rupture after blunt trauma.

BACKGROUND: Delayed splenic rupture (DSR) is a rare manifestation of blunt splenic trauma, and splenectomy remains the primary treatment for patients with DSR. The purpose of this study was to review our experience with nonsurgical management of DSR with the use of splenic artery embolization (SAE) as an adjunct treatment. METHODS: This retrospective study included patients with DSR treated at our institution from January 2001 to December 2008. Management included initial resuscitation and close observation in the intensive care unit. Further interventions were based on the patients hemodynamic status and followed a treatment protocol. These interventions included SAE or surgery. RESULTS: There were 15 patients included in the analysis. Three patients underwent emergent surgery, and 12 patients received nonsurgical management initially. Of these 12 patients, five underwent SAE. One of these five patients subsequently underwent splenectomy because of recurrent bleeding. Of the remaining seven patients who received nonoperative management, one required a splenectomy because of recurrent hemorrhage and hypotension. There were no mortalities; however, two surgery-associated complications occurred. The success rate of nonsurgical therapy was 83%. SAE was used for splenic salvage with a success rate of 80% (4 of 5). The overall failure rate of DSR was 33% (5 of 15). CONCLUSIONS: Nonsurgical management can safely be used in selected patients with DSR, especially for those with a good response to resuscitation. SAE is as effective for DSR as it is for acute splenic injury. Physicians should consider SAE as an option for the treatment of DSR. LEVEL OF EVIDENCE: IV, prognostic study.

Antithrombin-III attenuates hepatocyte apoptosis in bile duct ligated rat: a striking cellular change.

Background and purpose: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. This study was designed with the purpose of evaluating the possible effect of antithrombin-III on hepatocyte apoptosis in bile duct ligated rat. Materials and methods: The rats were randomized to 3 groups: group 1 (control, C) underwent sham operation; group 2 (obstructive jaundice, OB) underwent common bile duct ligation; and group 3 (obstructive jaundice with antithrombin-III, OBAT-III) underwent common bile duct ligation and simultaneously were treated with antithrombin-III. Liver tissues were harvested on the fifth postoperative day. Results: Hepatocyte apoptosis was significantly increased in bile duct ligated group when compared with the sham operation group. The administration of antithrombin-III effectively attenuates such phenomenon in obstructive jaundice with antithrombin-III group. Conclusion: Bile duct ligation significantly increased hepatocyte apoptosis and the administration of antithrombin-III effectively attenuates such phenomenon.

The kinetic expression of lipopolysaccharide-binding protein and CD14 gene in obstructive jaundice.

ABSTRACT Background: Binding lipopolysaccharide (LPS) with high-affinity, lipopolysaccharide-binding protein (LBP) and CD14 lower the threshold stimulatory concentrations of LPS dramatically and enhance the rate of cytokine production markedly. This study aimed to investigate the kinetic expression of LBP/CD14 and its possible relationship with tumor necrosis factor alpha (TNF-α) to better understand the pathophysiology of obstructive jaundice. Materials and Methods: The tissues (liver, spleen, intestine, and lung) of male Sprague-Dawley rats were harvested at pre-bile duct ligation in controls and at specific time points (24, 48, 72, 96, and 120 hr) after bile duct ligation. LBP, CD14, and TNF-α mRNA expression were measured in tissues harvested from controls and at the specific time points. Results: Hepatic LBP mRNA expression increased significantly at five days after bile duct ligation. CD 14 mRNA expression increased significantly after five days of bile duct ligation in liver, lung, spleen, and ileum. TNF-α mRNA expression increased significantly in all four organs (liver, lung, spleen, and ileum) after four days of bile duct ligation. Conclusion: Five days of bile duct ligation upregulated CD 14 mRNA expression in liver, lung, spleen, and ileum and increased TNF-α mRNA expression simultaneously in the liver, lung, spleen, and ileum. In addition, five days of bile duct ligation also upregulated LBP mRNA expression in the liver and increased hepatic TNF-α mRNA expression simultaneously. The kinetic expressions of LBP and CD 14 in obstructive jaundice are intriguing and further evaluation is warranted.