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J Pediatr Surg. 2014 Dec;49(12):1738-41. doi: 10.1016/j.jpedsurg.2014.09.009. Epub 2014 Nov 13.

MicroRNA-21/PTEN/Akt axis in the fibrogenesis of biliary atresia.

Author information

1
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: doc_albert@126.com.
2
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: chengongzlp@hotmail.com.
3
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: dongrui_1982@126.com.
4
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: zhao007rui007@sina.com.
5
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: szheng@shmu.edu.cn.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) are short, noncoding RNA molecules that act as post-transcriptional negative regulators of target mRNAs. Increasing evidence suggests that miRNAs are involved in liver fibrotic processes. Biliary atresia (BA) is characterized by rapid and progressive liver fibrosis. Therefore, we investigated the role of miRNA-21in the pathogenesis of BA.

METHODS:

We collected liver samples from patients with BA or liver trauma to examine the role of miRNA-21. We examined RNA expression of miRNA-21, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and α-smooth muscle actin (α-SMA) in liver tissue using real-time fluorescence quantitative PCR. Western blot analyses and immunohistochemical staining were performed to evaluate protein expression of PTEN, α-SMA, and phosphorylated AKT in liver.

RESULTS:

We found that miRNA-21was upregulated in liver samples from BA patients, whereas PTEN negatively correlated with suppression of the 3'-untranslated region (3'-UTR). Activation of the downstream AKT pathway provoked liver fibrosis by enhancing α-SMA levels.

CONCLUSIONS:

The miRNA-21/PTEN/AKT axis promotes the fibrosis process in BA, which might be a potential therapeutic target to improve the prognosis of patients with BA.

KEYWORDS:

Biliary atresia; Liver fibrosis; MicroRNA

PMID:
25487473
DOI:
10.1016/j.jpedsurg.2014.09.009
[Indexed for MEDLINE]

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