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Hepatology International

, Volume 13, Issue 6, pp 814–825 | Cite as

MicroRNA-744/transforming growth factor β1 relationship regulates liver cirrhosis

  • Shuang Ren
  • Jiamei Chen
  • Qinglan Wang
  • Xuewei Li
  • Ying Xu
  • Xiao Zhang
  • Yongping Mu
  • Hua Zhang
  • Shuang HuangEmail author
  • Ping LiuEmail author
Original Article
  • 167 Downloads

Abstract

Background

MicroRNAs have added a new dimension to our understanding of liver cirrhosis (LC) and associated processes like the activation of hepatic stellate cells (HSCs).

Methods

Serum samples were collected from 40 LC patients and 30 healthy donors. CCl4-induced LC mouse model in vivo and in vitro human HSC LX-2 and murine HSC JS-1 cells were researched.

Results

The levels of serum microRNA (miR)-744 is inversely correlated with the severity of LC and is a reliable biomarker of LC. In CCl4-induced LC model, the abundance of miR-744 was reduced in both sera and livers compared with sham controls. Importantly, increasing miR-744 abundance with synthetic miR-744 Agomir alleviated liver fibrosis, a critical component of LC, while reducing miR-744 with Antagomir exacerbated it. To elucidate molecular mechanism underlying the suppressive role of miR-744 in LC, we observed that miR-744 and transforming growth factor β1 (TGFβ1) are inversely correlated in LC patients’ sera as well as sera/livers from CCl4-induced LC mice. We demonstrated that miR-744 Agomir downregulated the expression of TGFβ1 and further confirmed that TGFβ1 mRNA was a bona fide miR-744 target in HSCs. Moreover, miR-744 Agomir reduced the degree of F-actin formation and cell proliferation while miR-744 Antagomir promoted these events, suggesting that miR-744 is a negative regulator of HSC activation.

Conclusions

MiR-744-led suppression in HSC activation is most likely through TGFβ1 because exogenous TGFβ1 nearly negated miR-744 Agomir’s action. This study suggests that reduction of miR-744 is a reliable biomarker for LC and miR-744/TGFβ1 relationship is a key regulator of LC.

Keywords

Liver cirrhosis miRNA TGFβ1 Hepatic stellate cells miR-744 

Abbreviations

LC

Liver cirrhosis

HSC

Hepatic stellate cell

ECM

Extracellular matrix

miRNA

MicroRNA

UTR

Untranslated region

TGFβ

Transforming growth factor β

EMT

Epithelial-to-mesenchymal transition

CHB

Chronic hepatitis B

qRT-PCR

Quantitative reverse transcription polymerase chain reaction

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

SUTCM

Shanghai University of Traditional Chinese Medicine

CCl4

Carbon tetrachloride

PBS

Phosphate buffered saline

ANOVA

Analysis of variance

ROC

Receiver–operator characteristic

Notes

Acknowledgements

This work is supported by National Natural Science Foundation of China (No. 81530101), NIH CA187152 and CA222467.

Author contributions

SR, SH and PL designed research. SR, JC, XL, WF and XZ performed the experiments and analyzed the data. YM, HZ, MS and CL contributed experimental materials or provided helpful suggestions. SR, JC, SH and PL wrote the manuscript.

Compliance with ethical standards

Conflict of interest

Shuang Ren, Jiamei Chen, Qinglan Wang, Xuewei Li, Ying Xu, Xiao Zhang, Yongping Mu, Hua Zhang, Shuang Huang, Ping Liu have no confict of interest to declare.

Ethics approval

Ethics approval all procedures performed in studies involving human participants and animals were in accordance with the ethical standards of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine. The entire study was approved by Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine.

Informed consent

Informed consent was collected from patients to approve utilization of their samples for research purposes.

Supplementary material

12072_2019_9993_MOESM1_ESM.jpg (193 kb)
Supplementary material 1 (JPEG 193 kb)
12072_2019_9993_MOESM2_ESM.pdf (113 kb)
Supplementary material 2 (PDF 112 kb)

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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  1. 1.Key Laboratory of Liver and Kidney Diseases (Ministry of Education)Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
  2. 2.Traditional Chinese Medicine DepartmentFirst Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Department of Anatomy and Cell BiologyUniversity of Florida College of MedicineGainesvilleUSA

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