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MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis by Regulating TGF-β1/smad Pathway.
J Immunol Res. 2021; 2021:6890423.JI

Abstract

BACKGROUND AND AIMS

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease. We found microRNA-34a (miR-34a), as the downstream gene of p53, was overexpressed in some of fibrogenic diseases. In this study, we sought to explore whether miR-34a plays a role in the fibrosis of PBC.

METHODS

The peripheral blood of PBC patients and controls was collected to analyze the level of miR-34a. Human intrahepatic biliary epithelial cells (HIBEC) were cultured. The expression of miR-34a was regulated by miR-34a mimics and inhibitor. The biomarkers of epithelium-mesenchymal transition (EMT), fibrogenesis, inflammation, and transforming growth factor- (TGF-) β1/smad pathway were analyzed.

RESULTS

We found that miR-34a was overexpressed in the peripheral blood in PBC patients. In vitro, overexpressed miR-34a increased the EMT and fibrogenesis activity of HIBEC. Transforming growth factor-beta type 1 receptor (TβR1), TGF-β1, and p-smad2/3 were upregulated by miR-34a. Inflammatory factors such as IL-6 and IL-17 were also upregulated. Finally, we showed that miR-34a promoted EMT and liver fibrosis in PBC by targeting the TGF-β1/smad pathway antagonist transforming growth factor-beta-induced factor homeobox 2 (TGIF2).

CONCLUSIONS

Our findings show that miR-34a plays an important role in the EMT and fibrosis of PBC through the TGF-β1/smad pathway by targeting TGIF2. This study suggests that miR-34a may be a new marker of fibrogenesis in PBC. Inhibition of miR-34a may be a promising strategy in treating PBC and improving the prognosis of the disease.

Authors+Show Affiliations

Department of Rheumatology and Immunology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.Department of Rheumatology and Immunology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.Department of Rheumatology and Immunology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

33977112

Citation

Pan, Ying, et al. "MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis By Regulating TGF-β1/smad Pathway." Journal of Immunology Research, vol. 2021, 2021, p. 6890423.
Pan Y, Wang J, He L, et al. MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis by Regulating TGF-β1/smad Pathway. J Immunol Res. 2021;2021:6890423.
Pan, Y., Wang, J., He, L., & Zhang, F. (2021). MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis by Regulating TGF-β1/smad Pathway. Journal of Immunology Research, 2021, 6890423. https://doi.org/10.1155/2021/6890423
Pan Y, et al. MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis By Regulating TGF-β1/smad Pathway. J Immunol Res. 2021;2021:6890423. PubMed PMID: 33977112.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis by Regulating TGF-β1/smad Pathway. AU - Pan,Ying, AU - Wang,Jing, AU - He,Lan, AU - Zhang,Fengchun, Y1 - 2021/04/23/ PY - 2020/07/10/received PY - 2021/01/11/revised PY - 2021/04/13/accepted PY - 2021/5/12/entrez PY - 2021/5/13/pubmed PY - 2021/11/30/medline SP - 6890423 EP - 6890423 JF - Journal of immunology research JO - J Immunol Res VL - 2021 N2 - BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease. We found microRNA-34a (miR-34a), as the downstream gene of p53, was overexpressed in some of fibrogenic diseases. In this study, we sought to explore whether miR-34a plays a role in the fibrosis of PBC. METHODS: The peripheral blood of PBC patients and controls was collected to analyze the level of miR-34a. Human intrahepatic biliary epithelial cells (HIBEC) were cultured. The expression of miR-34a was regulated by miR-34a mimics and inhibitor. The biomarkers of epithelium-mesenchymal transition (EMT), fibrogenesis, inflammation, and transforming growth factor- (TGF-) β1/smad pathway were analyzed. RESULTS: We found that miR-34a was overexpressed in the peripheral blood in PBC patients. In vitro, overexpressed miR-34a increased the EMT and fibrogenesis activity of HIBEC. Transforming growth factor-beta type 1 receptor (TβR1), TGF-β1, and p-smad2/3 were upregulated by miR-34a. Inflammatory factors such as IL-6 and IL-17 were also upregulated. Finally, we showed that miR-34a promoted EMT and liver fibrosis in PBC by targeting the TGF-β1/smad pathway antagonist transforming growth factor-beta-induced factor homeobox 2 (TGIF2). CONCLUSIONS: Our findings show that miR-34a plays an important role in the EMT and fibrosis of PBC through the TGF-β1/smad pathway by targeting TGIF2. This study suggests that miR-34a may be a new marker of fibrogenesis in PBC. Inhibition of miR-34a may be a promising strategy in treating PBC and improving the prognosis of the disease. SN - 2314-7156 UR - https://www.unboundmedicine.com/medline/citation/33977112/MicroRNA_34a_Promotes_EMT_and_Liver_Fibrosis_in_Primary_Biliary_Cholangitis_by_Regulating_TGF_β1/smad_Pathway_ L2 - https://doi.org/10.1155/2021/6890423 DB - PRIME DP - Unbound Medicine ER -