Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

Ikegami, Tadashi; Matsuzaki, Yasushi; Fukushima, Sugano; Shoda, Junichi; Olivier, Jean‐Luc; Bouscarel, Bernard; Tanaka, Naomi

doi:10.1002/hep.20630

Cited by 28 publications

(23 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SDS-PAGE (10% acrylamide gel) and Western blotting were performed as previously described. 24 Small Interfering RNA Transfection. Twenty-one sequences of nucleotide RNA were chemically synthe-sized by Qiagen (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of integrin-linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

et al. 2006

Self Cite

View full text Add to dashboard Cite

Integrin-linked kinase (ILK) is a multidomain focal adhesion protein implicated in signal transduction between integrins and growth factor receptors. Although its expression is upregulated in pulmonary and renal fibrosis, its role in the development of hepatic fibrosis remains to be determined. Therefore, we considered it important to investigate whether ILK is involved in activation of hepatic stellate cells and thus plays a role in the development of hepatic fibrosis. Immunohistochemical analysis of liver sections obtained from rats with CCl 4 -induced cirrhosis revealed increased expression and colocalization of ILK and alpha-smooth muscle actin in hepatic stellate cells in perisinusoidal areas. In addition, hepatic stellate cells isolated from fibrotic livers expressed high levels of ILK and alpha-smooth muscle actin, and their expression was sustained in culture. In contrast, hepatic stellate cells (HSCs) isolated from normal rat liver did not express ILK, but its expression was increased when the cells were activated in culture. Our studies also showed that ILK is involved in the phosphorylation of ERK 1/2, p38 MAPK, JNK, and PKB and that selective inhibition of ILK expression by siRNA results in a significant decrease in their phosphorylation. These changes were accompanied by significant inhibition of cell spreading and migration without affecting cell proliferation. In conclusion, ILK plays a key role in HSC activation and could be a possible target for antifibrogenic therapy. (HEPATOLOGY 2006;44:612-622.)

show abstract

Section: Methodsmentioning

confidence: 99%

“…CFSC-2G cells were transfected with siRNA using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) according to the manufacturer's protocol as previously described. 24 Cells were used 48 hours after transfection. In addition, a Nucleofection apparatus (Amaxa, Cologne, Germany) was used for transfection of the HSCs in primary culture.…”

Section: Methodsmentioning

confidence: 99%

Involvement of integrin-linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, TUDC in hamster hepatocytes inhibits cAMP synthesis by glucagon [11] and UDC inhibits the interleukin (IL)-6 induction of phospholipase (PL)A 2 IIa expression at the transcriptional level in HepG2 cells [12]. As shown recently, in perfused rat liver, rat hepatocytes and HepG2 cells GCDC stimulates a caspase-dependent cleavage of gp130, which was prevented by TUDC [13].…”

Section: Introductionmentioning

confidence: 93%

Taurolithocholic Acid-3 Sulfate Impairs Insulin Signaling in Cultured Rat Hepatocytes and Perfused Rat Liver

Mannack

Graf²,

Donner³

et al. 2008

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The role of bile acids for insulin resistance in cholestatic liver disease is unknown. Methods: The effect of taurolithocholic acid-3 sulfate (TLCS) on insulin signaling was studied in cultured rat hepatocytes and perfused rat liver. Results: TLCS induced insulin resistance at the level of insulin receptor (IR) β Tyr(1158) phosphorylation, phosphoinositide (PI) 3-kinase activity and protein kinase (PK)B Ser(473) phosphorylation in cultured hepatocytes. Consistently, the insulin stimulation of the PI 3-kinase-dependent K⁺ uptake, hepatocyte swelling and proteolysis inhibition was blunted by TLCS in perfused rat liver. The PKC inhibitor Gö6850 and tauroursodeoxycholate (TUDC) counteracted the suppression of insulin-induced IRβ and PKB phosphorylation by TLCS. Rapamycin and dibutyryl-cAMP, which inhibited basal signaling via mammalian target of rapamycin (mTOR), restored insulin-induced PKB- but not IRβ phosphorylation. In livers from 7 day bile duct-ligated rats PKB Ser(473) phosphorylation was decreased by about 50%. Conclusion: TLCS induces insulin resistance by a PKC-dependent suppression of insulin-induced IRβ phosphorylation and the PI 3-kinase/PKB path. This can in part be compensated by a decrease of mTOR activity, which may release insulin-sensitive components downstream of the insulin receptor from tonic inhibition. The data suggest that retention of hydrophobic bile acids confers insulin resistance on the cholestatic liver.

show abstract

“…We therefore concluded that serum UDCA concentrations should adjusted through dosage modifications to achieve the required effect [345] . UDCA is an extraordinary molecule since apart from the action mentioned above it seems likely, that it exerts anti-inflammatory [346] and immunological protective effects as well. UDCA strongly reduced MHC class Ⅰ expression in the liver in PBC [347] .…”

Section: Mode Of Action Of Udcamentioning

confidence: 99%

Primary biliary cirrhosis: From bench to bedside

Notas

2015

WJGPT

View full text Add to dashboard Cite

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. Core tip: Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis of largely unknown pathophysiology. We examined the epidemiological and geoepidemiological data as well as the pathogenetic aspects of PBC. A novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.

show abstract

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

Cited by 28 publications

References 49 publications

Involvement of integrin-linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

Involvement of integrin-linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

Taurolithocholic Acid-3 Sulfate Impairs Insulin Signaling in Cultured Rat Hepatocytes and Perfused Rat Liver

Primary biliary cirrhosis: From bench to bedside

Contact Info

Product

Resources

About