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Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

ABSTRACT: To investigate the effects of hyperbaric oxygenation (HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized rats.HBO was performed in Wistar rats daily starting 12 h after a 70% partial hepatectomy. Regenerated liver weight, serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were measured. Hepatocyte growth factor (HGF), c-Met and transforming growth factor (TGF) ?-1 mRNA expression levels were analyzed by quantitative reverse transcription polymerase chain reaction.HBO improved the postoperative serum levels of total bile acid but not transaminase levels. HBO promoted hepatocyte and biliary ductal cell proliferation. The hematoxylin and eosin-stained specimens revealed fewer ballooned hepatocytes and higher cell densities in the HBO group compared to the control group. HBO suppressed c-Met mRNA levels at 15 h but did not modulate HGF or TGF ?-1 mRNA expression levels.HBO promoted regeneration of biliary ductal cells and improved postoperative cholestasis after a partial hepatectomy.

SUBMITTER: Idetsu A

PROVIDER: S-EPMC3092876 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

Idetsu Akihito A Suehiro Taketoshi T Okada Kohji K Shimura Tatsuo T Kuwano Hiroyuki H

World journal of gastroenterology 20110501 17

<h4>Aim</h4>To investigate the effects of hyperbaric oxygenation (HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized rats.<h4>Methods</h4>HBO was performed in Wistar rats daily starting 12 h after a 70% partial hepatectomy. Regenerated liver weight, serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were measured. Hepatocyte growth factor (HGF), c-Met and transforming growth factor (TGF ...[more]

PMID: 21633534

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Project description:Whether hepatocytes can convert into biliary epithelial cells (BECs) during biliary injury is much debated. To test this concept, we traced the fate of genetically labeled [dipeptidyl peptidase IV (DPPIV)-positive] hepatocytes in hepatocyte transplantation model following acute hepato-biliary injury induced by 4,4'-methylene-dianiline (DAPM) and D-galactosamine (DAPM+D-gal) and in DPPIV-chimeric liver model subjected to acute (DAPM+D-gal) or chronic biliary injury caused by DAPM and bile duct ligation (DAPM+BDL). In both models before biliary injury, BECs are uniformly DPPIV-deficient and proliferation of DPPIV-deficient hepatocytes is restricted by retrorsine. We found that mature hepatocytes underwent a stepwise conversion into BECs after biliary injury. In the hepatocyte transplantation model, DPPIV-positive hepatocytes entrapped periportally proliferated, and formed two-layered plates along portal veins. Within the two-layered plates, the hepatocytes gradually lost their hepatocytic identity, proceeded through an intermediate state, acquired a biliary phenotype, and subsequently formed bile ducts along the hilum-to-periphery axis. In DPPIV-chimeric liver model, periportal hepatocytes expressing hepatocyte nuclear factor-1β (HNF-1β) were exclusively DPPIV-positive and were in continuity to DPPIV-positives bile ducts. Inhibition of hepatocyte proliferation by additional doses of retrorsine in DPPIV-chimeric livers prevented the appearance of DPPIV-positive BECs after biliary injury. Moreover, enriched DPPIV-positive BEC/hepatic oval cell transplantation produced DPPIV-positive BECs or bile ducts in unexpectedly low frequency and in mid-lobular regions. These results together suggest that mature hepatocytes but not contaminating BECs/hepatic oval cells are the sources of periportal DPPIV-positive BECs. We conclude that mature hepatocytes contribute to biliary regeneration in the environment of acute and chronic biliary injury through a ductal plate configuration without the need of exogenously genetic or epigenetic manipulation.

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Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

Publications

Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

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