Theranostics 2021; 11(15):7600-7615. doi:10.7150/thno.47845 This issue Cite

Research Paper

Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p

Hongmei Zhao1*, Hongqin Yang1*, Chi Geng1*, Yang Chen1, Yaqin Tang1, Zhiwei Li1, Junling Pang1, Ting Shu1, Yu Nie2, Yongshuo Liu3,4, Kegang Jia5, Jing Wang1✉

1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing 100005, China.
2. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 102308, China.
3. Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
4. Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
5. Department of Clinical Laboratory, TEDA International Cardiovascular Hospital, Tianjin 300457, China.
*These authors contributed equally to this work.

Citation:
Zhao H, Yang H, Geng C, Chen Y, Tang Y, Li Z, Pang J, Shu T, Nie Y, Liu Y, Jia K, Wang J. Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p. Theranostics 2021; 11(15):7600-7615. doi:10.7150/thno.47845. https://www.thno.org/v11p7600.htm
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Abstract

Graphic abstract

Rationale: Cardiac fibrosis is an important feature of cardiac remodeling and is a hallmark of heart failure. Recent studies indicate that elevated IgE plays a causal role in pathological cardiac remodeling. However, the underlying mechanism of how IgE promotes cardiac fibrosis has not been fully elucidated.

Methods and Results: To explore the function of IgE in cardiac fibrosis, we stimulated mouse primary cardiac fibroblasts (CFs) with IgE and found that both IgE receptor (FcεR1) and fibrosis related proteins were increased after IgE stimulation. Specific deletion of FcεR1 in CFs alleviated angiotensin II (Ang II)-induced cardiac fibrosis in mice. To investigate the mechanisms underlying the IgE-mediated cardiac fibrosis, deep miRNA-seq was performed. Bioinformatics and signaling pathway analysis revealed that IgE upregulated Col1a1 and Col3a1 expression in CFs by repressing miR-486a-5p, with Smad1 participating downstream of miR-486a-5p in this process. Lentivirus-mediated overexpression of miR-486a-5p was found to alleviate Ang II-induced myocardial interstitial fibrosis in mice. Moreover, miR-486-5p serum levels were lower in patients with heart failure than in healthy controls, and were negatively correlated with NT-proBNP levels.

Conclusions: Our study demonstrates that elevated IgE promotes pathological cardiac fibrosis by modulating miR-486a-5p and downstream factors, such as Smad1. These findings suggest new targets for pathological cardiac fibrosis intervention.

Keywords: cardiac fibrosis, IgE, FcεR1, microRNAs, cardiac fibroblasts


Citation styles

APA
Zhao, H., Yang, H., Geng, C., Chen, Y., Tang, Y., Li, Z., Pang, J., Shu, T., Nie, Y., Liu, Y., Jia, K., Wang, J. (2021). Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p. Theranostics, 11(15), 7600-7615. https://doi.org/10.7150/thno.47845.

ACS
Zhao, H.; Yang, H.; Geng, C.; Chen, Y.; Tang, Y.; Li, Z.; Pang, J.; Shu, T.; Nie, Y.; Liu, Y.; Jia, K.; Wang, J. Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p. Theranostics 2021, 11 (15), 7600-7615. DOI: 10.7150/thno.47845.

NLM
Zhao H, Yang H, Geng C, Chen Y, Tang Y, Li Z, Pang J, Shu T, Nie Y, Liu Y, Jia K, Wang J. Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p. Theranostics 2021; 11(15):7600-7615. doi:10.7150/thno.47845. https://www.thno.org/v11p7600.htm

CSE
Zhao H, Yang H, Geng C, Chen Y, Tang Y, Li Z, Pang J, Shu T, Nie Y, Liu Y, Jia K, Wang J. 2021. Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p. Theranostics. 11(15):7600-7615.

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