Altered expression of alkaline phosphatase (ALP) in the liver of primary biliary cirrhosis (PBC) patients

Suzuki, Norihisa; Irie, Makoto; Iwata, Kazuo; Nakane, Hidetoshi; Yoshikane, Makoto; Koyama, Yasuhiro; Uehara, Yuko; Takeyama, Yoshifumi; Kitamura, Yuji; Sohda, Tetsuro; Watanabe, Hiroshi; Ikehara, Yukio; Sakisaka, Shotaro

doi:10.1016/j.hepres.2006.01.009

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…Alkaline phosphatase is normally located in the canalicular membrane of hepatocytes and in apical cholangiocyte cytoplasm; in patients with PBC, however, alkaline phosphatase was also found in the basolateral membrane of hepatocytes and throughout the cytoplasm of cholangiocytes, in association with increased alkaline-phosphatase protein and mRNA levels in liver tissue. 36 In some forms of intrahepatic cholestasis, g-GT expression along canaliculi appears disordered or lacking, and g-GTA in patients with those disorders does not rise despite cholestasis. 37,38 Our study demonstrates that variation in hepatobiliary CD10 expression may account for variation in conclusions drawn from previous studies of whether NEA can mark cholestasis.…”

Section: Nc1 Ags1 Ags2 Ags4 Ags5mentioning

confidence: 99%

Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome

Byrne

Meara

Rayner

et al. 2007

Laboratory Investigation

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Many tissues, including hepatobiliary cells, express neutral endopeptidase (CD10), encoded by MME. Serum neutral endopeptidase activity (NEA) has been recommended as a marker of cholestasis in adults but not in children with Alagille syndrome (AGS). We investigated ontogenic and disease-related differences in the expression of CD10. CD10 was found on canalicular surfaces of hepatocytes throughout the lobule in 16 adults and in 31 children aged Z24 months, with and without cholestasis, but not in 39 children aged o24 months, with and without cholestasis. Ten AGS children aged 2 months to 6 years lacked any canalicular CD10 expression. Cholangiocyte apices and/or intrasinusoidal granulocytes marked for CD10 in all subjects. Liver membrane fractions from a child with cholestasis aged o24 months and from 2 AGS patients aged 424 months contained reduced levels of CD10. In contrast, AGS children and all controls expressed CD10 similarly on granulocytes. MME mRNA was found in the liver of children aged o24 months and of adults, all with cholestasis, and of AGS patients. Granulocyte MME mRNA levels were similar among all study subjects; however, liver MME mRNA levels were 6-to 140-fold less than in normal adults in all cholestatic subjects, including AGS children. Methylation of the MME promoter was not detected in the liver of AGS children. In conclusion, hepatocytes in early childhood physiologically lack immunohistochemically detectable CD10. Reduced MME mRNA in AGS is not due to MME promoter methylation. Liver CD10 in childhood appears to undergo reduced synthesis or rapid degradation, which persists in AGS. Absence of CD10 expression thus may limit NEA as a marker of cholestasis in young patients and in AGS.

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Section: Nc1 Ags1 Ags2 Ags4 Ags5mentioning

confidence: 99%

Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome

Byrne

Meara

Rayner

et al. 2007

Laboratory Investigation

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“…Primary biliary cirrhosis (PBC) is a disease of unknown cause in which intrahepatic bile ducts are progressively destroyed by biliary epithelial cells (BEC) apoptosis 2,3 . In PBC patients, our previous studies showed the diminished tight junction of BEC, 4 the enhanced expression of heat shock protein 70 (HSP 70), 5 and the altered localization of alkaline phosphatase (ALP) in the liver 6 . PBC is characterized by chronic inflammation that targets mainly the small bile ducts, resulting in duct destruction (ductopenia) and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Hepatobiliary membrane transporters in primary biliary cirrhosis

Takeyama

Sakisaka

2011

Hepatology Research

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The secretion of bile normally depends on the function of a number of membrane transport systems in hepatocytes and cholangiocytes. The transport of solutes from the blood to the bile is driven by transport systems in the plasma membrane of the basolateral and canalicular surfaces of the hepatocytes. In cholestatic animal models, the expression of hepatobiliary transporters changes in response to functional impairment of the efflux of bile salts and various organic anions. In recent years, several studies have led to an improved understanding of the function and regulation of hepatobiliary transport systems in patients with primary biliary cirrhosis (PBC). This review focuses on the adaptations in hepatobiliary transporters in PBC patients.

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“…Thus, GGT correlated inversely with PHA and ALP correlated inversely with BEA. Both enzymes are localized to BECs and the canalicular membrane of the hepatocyte . This observation of biochemical values reflecting actual microscopic events in the porta hepatis appears to be original.…”

Section: Discussionmentioning

confidence: 62%

“…Both enzymes are localized to BECs and the canalicular membrane of the hepatocyte. [21][22][23] This observation of biochemical values reflecting actual microscopic events in the porta hepatis appears to be original. Its pathogenesis and clinical implications are uncertain.…”

Section: Discussionmentioning

confidence: 99%