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LncRNA MAAMT facilitates macrophage recruitment and proinflammatory activation and exacerbates autoimmune myocarditis through the SRSF1/NF-κB axis.
Gan, Ting; Liu, Wenhu; Wang, Yan; Huang, Dan; Hu, Jing; Wang, Ya; Xiong, Jingjie; Wang, Xuehua; Xu, Qian; Xiong, Ni; Lu, Shuai; Wang, Zhaohui.
Afiliación
  • Gan T; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Liu W; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Wang Y; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Huang D; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Hu J; Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • Wang Y; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Xiong J; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Wang X; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Xu Q; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Xiong N; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
  • Lu S; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: lsluckyhuster@163.com.
  • Wang Z; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei
Int J Biol Macromol ; 278(Pt 1): 134193, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39069042
ABSTRACT
Long non-coding RNAs (lncRNAs) have been implicated in dilated cardiomyopathy (DCM). However, the biological functions and regulatory mechanisms of lncRNAs in DCM remain elusive. Using a mouse model of experimental autoimmune myocarditis (EAM) to mimic DCM, we successfully constructed a dynamic lncRNA expression library for EAM by lncRNA microarray and found that the expression of a macrophage-enriched lncRNA, MAAMT, was significantly increased in the myocardial tissue of mice at the acute stage of EAM. Functionally, MAAMT knockdown alleviated the recruitment and proinflammatory activation of macrophages in the heart, spleen, and peripheral blood of mice at the acute stage of EAM, reduced myocardial inflammation and injury, and eventually reversed ventricular remodelling and improved cardiac function in mice at the chronic stage of EAM. Mechanistically, we identified serine/arginine-rich splicing factor 1 (SRSF1) as an MAAMT-interacting protein in macrophages using RNA pull-down assays coupled with mass spectrometry. MAAMT knockdown attenuated the ubiquitination-mediated degradation of SRSF1, increased the protein expression of SRSF1, and restrained the activation of the NF-κB pathway in macrophages, thereby inhibiting the proinflammatory activation of macrophages. Collectively, our results demonstrate that MAAMT is a key proinflammatory regulator of myocarditis that promotes macrophage activation through the SRSF1-NF-κB axis, providing a new insight into early effective treatment strategies for DCM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Transducción de Señal / FN-kappa B / ARN Largo no Codificante / Factores de Empalme Serina-Arginina / Macrófagos / Miocarditis Límite: Animals Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Transducción de Señal / FN-kappa B / ARN Largo no Codificante / Factores de Empalme Serina-Arginina / Macrófagos / Miocarditis Límite: Animals Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos