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Transforming Growth Factor (TGF)-β-Induced MicroRNA-216a Promotes Acute Pancreatitis Via Akt and TGF-β Pathway in Mice

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Abstract

Background

Both transforming growth factor β (TGF-β) and MicroRNA-216a (miR-216a) were reported to be upregulated during acute pancreatitis (AP). Moreover, miR-216a can be induced by TGF-β.

Aim

This study aimed to investigate how TGF-β and miR-216a involved in the pathogenesis of AP both in a mouse model and in rat pancreatic acinar AR42J cells.

Methods

Cerulein-induced AP mouse model was established and pretreated with a TGF-β inhibitor, SB431542. Serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), TGF-β and histopathological changes of pancreas were determined. Expression of miR-216a was detected by quantitative real-time RT-PCR. Bioinformatics was utilized to predict the targets of miR-216a. Expression levels of phosphatase and tensin homolog (PTEN), mothers against decapentaplegic homolog 7 (Smad7), TGF-β receptor I, total Akt and pAkt were detected by Western blot.

Results

SB431542 significantly decreased serum amylase, lipase, TNF-α, IL-6, TGF-β, histopathological changes of pancreas and expression of miR-216a in cerulein-induced mouse (P < 0.05). TGF-β induced miR-216a in AR42J cells. PTEN and Smad7 were identified to be the possible targets of miR-216a. Transfection of miR-216a mimics (or inhibitors) in AR42J cells downregulated (or upregulated) the expression of PTEN and Smad7, thus affected the expression of downstream pAkt and TGF-β receptor I. The expression changes of these protein caused by miR-216a can be regulated by SB431542 both in mouse model and AR42J cells.

Conclusions

TGF-β promotes AP by inducing miR-216a targeting PTEN and Smad7, thus through PI3K/Akt and TGF-β feedback pathway.

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Acknowledgments

The study was supported by the National Natural Science Foundation of China (81370567) and Research Foundation for Middle-aged and Young Scientist in Shandong Province (BS2010SW006).

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Authors and Affiliations

  1. Department of General Surgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, People’s Republic of China

    Jian Zhang, Xianfeng Ning, Meisheng Bi, Dianliang Zhang & Jianli Zhang

  2. Department of General Surgery, Qingdao Municipal Hospital, 5 Donghaizhong Road, Qingdao, 266071, Shandong Province, People’s Republic of China

    Wei Cui

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  1. Jian Zhang
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  2. Xianfeng Ning
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Correspondence to Jian Zhang.

Additional information

Jianli Zhang, Xianfeng Ning and Wei Cui have contributed equally to this work.

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Zhang, J., Ning, X., Cui, W. et al. Transforming Growth Factor (TGF)-β-Induced MicroRNA-216a Promotes Acute Pancreatitis Via Akt and TGF-β Pathway in Mice. Dig Dis Sci 60, 127–135 (2015). https://doi.org/10.1007/s10620-014-3261-9

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  • DOI: https://doi.org/10.1007/s10620-014-3261-9

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