Brief Article
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World J Gastroenterol. Mar 21, 2014; 20(11): 3011-3017
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.3011
Hyperoxia accelerates progression of hepatic fibrosis by up-regulation of transforming growth factor-β expression
Sang Hwa Lee, Sung-Im Do, Hyun-Soo Kim
Sang Hwa Lee, Hyun-Soo Kim, Department of Pathology, Aerospace Medicine Research Center, Aerospace Medical Center, Republic of Korea Air Force, Chungcheongbuk-do 363-849, South Korea
Sung-Im Do, Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, South Korea
Author contributions: Lee SH and Do SI contributed equally to this work in the design of the study, acquisition of the data and interpretation of the results; Do SI provided vital reagents and analytical tools; Lee SH drafted the manuscript; Kim HS and Do SI revised the manuscript critically and provided vital guidance to the study; all authors approved the final version of the manuscript.
Supported by Aerospace Medicine Research Project funded by the Medical Division, Headquarter, Republic of Korea Air Force (2012)
Correspondence to: Hyun-Soo Kim, MD, Department of Pathology, Aerospace Medicine Research Center, Aerospace Medical Center, Republic of Korea Air Force, 635 Danjae-ro, Namil-myeon, Cheongwon-gun, Chungcheongbuk-do 363-849, South Korea. apkimhs@gmail.com
Telephone: +82-43-2905461 Fax: +82-43-2948951
Received: July 1, 2013
Revised: November 20, 2013
Accepted: January 6, 2014
Published online: March 21, 2014
Processing time: 259 Days and 16.9 Hours
Abstract

AIM: To investigate the effect of hypoxia or hyperoxia on the progression of hepatic fibrosis and to examine the role of transforming growth factor-β (TGF-β) in the livers of rats exposed to hypoxic or hyperoxic conditions.

METHODS: Male Sprague-Dawley rats were injected intraperitoneally with thioacetamide to induce hepatic fibrosis and were randomly divided into a hypoxia group, a hyperoxia group and an untreated control group. Ten rats in the hypoxia group were exposed to an altitude of 20000 ft for 1 h/d during 7 wk. Ten rats in the hyperoxia group were exposed to a water depth of 20 m with 100% oxygen supply for 1 h/d during 7 wk. We evaluated the degree of hepatic fibrosis using Masson trichrome stain and examined the expression level of hepatic TGF-β mRNA using quantitative real-time reverse transcriptase-polymerase chain reaction analysis.

RESULTS: Eight of 10 rats exposed to hypoxia showed diffuse and confluent fibrosis with the formation of structurally abnormal parenchymal nodules involving the entire liver, consistent with hepatic cirrhosis. Nine of 10 rats exposed to hyperoxia also demonstrated obvious histological findings of hepatic cirrhosis identical to those in hypoxic rat livers. In contrast, 8 of 10 untreated rats had periportal or septal fibrosis only. The frequency of hepatic cirrhosis in hypoxic rats (P = 0.009) and hyperoxic rats (P = 0.003) was significantly higher than that in untreated rats. In addition, hepatic TGF-β mRNA levels in hyperoxic rats were significantly higher than those in untreated rats. The mean value of the normalized TGF-β mRNA/β-actin expression ratio in the hyperoxic rats was 1.9-fold higher than that in the untreated rats (P = 0.027).

CONCLUSION: We demonstrated that both hypoxia and hyperoxia accelerated the progression of hepatic fibrosis in rats. Significant up-regulation of hepatic TGF-β in hyperoxic rats suggests that TGF-β is involved in the acceleration of hepatic fibrosis under hyperoxic conditions.

Keywords: Hepatic fibrosis; Cirrhosis; Hypoxia; Hyperoxia; Transforming growth factor-β

Core tip: We observed that both hypoxic and hyperoxic rat livers exhibited significantly higher frequencies of hepatic cirrhosis than untreated rat livers. We also observed that hepatic transforming growth factor-β (TGF-β) expression in hyperoxic rats was significant higher than that in untreated rats, suggesting that TGF-β is involved in the acceleration of hepatic fibrosis under hyperoxic conditions. To the best of our knowledge, up-regulated TGF-β expression in the livers of cirrhotic rats exposed to hyperoxia has not been reported.