Identification of transforming growth factors actively transcribed during the progress of liver fibrosis in biliary atresia

Transforming growth factor-beta (TGF-β) 1 and 2 and their receptors TβR-I, TβR-II, and TβR-III are powerful profibrogenic mediators in the body. Their expression has not been completely elucidated in the progress of liver fibrosis associated with biliary atresia (BA). The authors compared the cytoki...

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Bibliographic Details
Published in:Journal of pediatric surgery 2004-05, Vol.39 (5), p.702-708
Main Authors: Lee, Shin-Ye, Chuang, Jiin-Haur, Huang, Chao-Cheng, Chou, Ming-Huei, Wu, Chia-Ling, Chen, Ching-Mei, Hsieh, Chie-Song, Chen, Chao-Long
Format: Article
Language:English
Subjects:
Adolescent
Biliary atresia
Biliary Atresia - genetics
Biliary Atresia - metabolism
Biliary Atresia - pathology
Child, Preschool
DNA microarray
Female
human
Humans
immunohistochemistry
Infant
Liver - metabolism
Liver - pathology
Liver Cirrhosis - genetics
Liver Cirrhosis - metabolism
Liver Cirrhosis - pathology
liver fibrosis
Liver Transplantation
Male
Oligonucleotide Array Sequence Analysis
real-time quantitative reverse transcriptase polymerase chain reaction
receptor
Receptors, Transforming Growth Factor beta - genetics
Receptors, Transforming Growth Factor beta - metabolism
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
Transcription, Genetic
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta - blood
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta1
Transforming Growth Factor beta2
transforming growth factor-beta
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Summary:Transforming growth factor-beta (TGF-β) 1 and 2 and their receptors TβR-I, TβR-II, and TβR-III are powerful profibrogenic mediators in the body. Their expression has not been completely elucidated in the progress of liver fibrosis associated with biliary atresia (BA). The authors compared the cytokine expression in the liver of 3 patients with BA at Kasai’s procedure (KP) and in 3 patients at liver transplantation (LT). Two liver samples from children with no liver disorders served as normal controls (CO). Real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) was used to confirm the findings of relative mRNA expression of TGF-β1 and 2 and their receptors. An immunohistochemistry and an enzyme-linked immunoassay (ELISA) were used to localize the liver cells that express TGF-β2 and to quantitate the protein expression among groups. Compared with controls, both TGF-β1 and TGF-β2 mRNA expression increased in the liver during the progress of liver fibrosis in patients with KP and LT on the array. Only TGF-β2 showed a significant increase in expression in LT compared with KP and CO ( P = .001 for TGF-β2 and P = 0.054 for TGF-β1). Both TβR-I and TβR-II showed no significant change among groups; TβR-III decreased significantly in LT compared with CO ( P = .011). TGF-β2 immunostaining was mainly localized in the bile duct epithelium and was remarkably higher in LT in which the proliferating bile ductules and the hepatocytes contributed to the increase in immunostaining and possibly to significantly higher plasma TGF-β2 protein levels in LT than in KP. This study identified TGF-β2 as the most actively transcribed TGF-β gene during the progress of liver fibrosis in BA and found a reciprocal relationship of upregulation of TGF-β2 with downregulation of TβR-III in LT.
ISSN:0022-3468
1531-5037
DOI:10.1016/j.jpedsurg.2004.01.030