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CircScd1 Promotes Fatty Liver Disease via the Janus Kinase 2/Signal Transducer and Activator of Transcription 5 Pathway

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Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Recent studies have reported that circular RNAs (circRNAs) are important regulators of hepatic steatosis. However, the role and mechanism of circRNA in NAFLD are poorly understood.

Aims

This study is to reveal the role and mechanism of circRNA in NAFLD.

Methods

Through NAFLD-related circRNA microarrays, we used real-time quantitative reverse transcription-polymerase chain reaction to screen circScd1 levels in control and test groups of mice fed a high-fat diet. RNA interference and over-expression plasmid vectors were used to manipulate the expression of circScd1, and the biological effects were evaluated by oil red staining, triglyceride detection, and western blot analysis.

Results

CircScd1 expression was significantly lower in NAFLD tissues than in control tissues. Moreover, over-expression of circScd1 significantly inhibited the formation of lipid droplets. Western blot analyses showed that the protein levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were significantly increased. However, knockdown of circScd1 significantly promoted the degree of hepatocellular lipidosis and reduced the expression levels of JAK2 and STAT5.

Conclusions

Aberrant expression of circScd1 affects the extent of hepatocellular lipidosis in NAFLD and promotes fatty liver disease via the JAK2/STAT5 pathway.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

JAK2:

Janus kinase 2

STAT5:

Signal transducer and activator of transcription 5

NASH:

Nonalcoholic steatohepatitis

SD:

Standard diet

HFD:

Fed with high-fat diet

DMEM:

Dulbecco’s modified Eagle medium

FBS:

Fetal bovine serum

PA:

Palmitic acid

BSA:

Bovine serum albumin

qRT-PCR:

Real-time quantitative reverse transcription-polymerase chain reaction

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

SiRNA:

Small interfering RNA

S.D.:

Standard deviation

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Acknowledgments

This work was supported by the Zhejiang Provincial Natural Science Foundation of China (Nos. LQ18H160015 to P.L. and LY13H030012 to L.X.), the National Natural Science Foundation of China (No. 81300703 to L.X.), and the Ningbo Natural Science Foundation of China (Nos. 2015A610183 and 2015A610178).

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Authors and Affiliations

  1. Department of Gastroenterology, Ningbo First Hospital, 59 Liuting Street, Ningbo, 315010, China

    Peifei Li, Keshu Shan, Yi Liu & Lei Xu

  2. Ningbo University School of Medicine, No 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China

    Yu Zhang & Lu Xu

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  1. Peifei Li
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  2. Keshu Shan
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  3. Yi Liu
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  4. Yu Zhang
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  5. Lu Xu
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Correspondence to Lei Xu.

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Li, P., Shan, K., Liu, Y. et al. CircScd1 Promotes Fatty Liver Disease via the Janus Kinase 2/Signal Transducer and Activator of Transcription 5 Pathway. Dig Dis Sci 64, 113–122 (2019). https://doi.org/10.1007/s10620-018-5290-2

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  • DOI: https://doi.org/10.1007/s10620-018-5290-2

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