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ADAR1 promotes systemic sclerosis via modulating classic macrophage activation.
Sun, Chenming; Cai, Dunpeng; Chen, Shi-You.
Afiliação
  • Sun C; Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Cai D; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
  • Chen SY; Xi'an Key Laboratory of Immune Related Diseases, Xi'an, Shaanxi, China.
Front Immunol ; 13: 1051254, 2022.
Article em En | MEDLINE | ID: mdl-36532023
ABSTRACT

Introduction:

As a multisystem autoimmune disorder disease, systemic sclerosis (SSc) is characterized by inflammation and fibrosis in the skin and other internal organs. However, mechanisms underlying the inflammatory response that drives the development of SSc remain largely unknown.

Methods:

ADAR1 heterozygous knockout (AD1+/-) mice and myeloid-specific ADAR1 knockout mice were used to determine the function of ADAR1 in SSc. Histopathological analyses and western blot confirmed the role of ADAR1 in bleomycin-induced increased skin and lung fibrosis.

Results:

In this study, we discover that adenosine deaminase acting on RNA (ADAR1), a deaminase converting adenosine to inosine (i.e., RNA editing) in RNA, is abundantly expressed in macrophages in the early stage of bleomycin-induced SSc. Importantly, ADAR1 is essential for SSc formation and indispensable for classical macrophage activation because ADAR1 deficiency in macrophages significantly ameliorates skin and lung sclerosis and inhibits the expression of inflammation mediator inducible NO synthase (iNOS) and IL-1ß in macrophages. Mechanistically, deletion of ADAR1 blocks macrophage activation through diminishing NF-κB signaling.

Discussion:

Our studies reveal that ADAR1 promotes macrophage activation in the onset of SSc. Thus, targeting ADAR1 could be a potential novel therapeutic strategy for treating sclerosis formation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Escleroderma Sistêmico / Ativação de Macrófagos Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Escleroderma Sistêmico / Ativação de Macrófagos Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article