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STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis.
Am J Physiol Heart Circ Physiol. 2019 09 01; 317(3):H531-H540.AJ

Abstract

As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM.NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis.

Authors+Show Affiliations

Department of Cardiovascular Disease Center, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.Department of Echocardiography, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.Department of Geriatrics, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.Department of Cardiovascular Medicine, The Eastern Division of the First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31225989

Citation

Pan, Aiqun, et al. "STAT4 Silencing Underlies a Novel Inhibitory Role of microRNA-141-3p in Inflammation Response of Mice With Experimental Autoimmune Myocarditis." American Journal of Physiology. Heart and Circulatory Physiology, vol. 317, no. 3, 2019, pp. H531-H540.
Pan A, Tan Y, Wang Z, et al. STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis. Am J Physiol Heart Circ Physiol. 2019;317(3):H531-H540.
Pan, A., Tan, Y., Wang, Z., & Xu, G. (2019). STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis. American Journal of Physiology. Heart and Circulatory Physiology, 317(3), H531-H540. https://doi.org/10.1152/ajpheart.00048.2019
Pan A, et al. STAT4 Silencing Underlies a Novel Inhibitory Role of microRNA-141-3p in Inflammation Response of Mice With Experimental Autoimmune Myocarditis. Am J Physiol Heart Circ Physiol. 2019 09 1;317(3):H531-H540. PubMed PMID: 31225989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis. AU - Pan,Aiqun, AU - Tan,Yuying, AU - Wang,Zhihao, AU - Xu,Guoliang, Y1 - 2019/06/21/ PY - 2019/6/22/pubmed PY - 2020/3/24/medline PY - 2019/6/22/entrez KW - STAT4 KW - autoimmune myocarditis KW - cardiac function KW - inflammatory response KW - microRNA-141-3p SP - H531 EP - H540 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 317 IS - 3 N2 - As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM.NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/31225989/STAT4_silencing_underlies_a_novel_inhibitory_role_of_microRNA_141_3p_in_inflammation_response_of_mice_with_experimental_autoimmune_myocarditis_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpheart.00048.2019?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -