MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis

Wei Zhu, Jianbo Yu, Shou Qiu, Haifeng Liu, Yan Wang, Xiaoyan Xu, Lili Shao, Lingling Zhu, Yan Jiao, Fan Liu, Xiaodong Zhu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160 IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalInternational Immunopharmacology
Volume51
DOIs
StatePublished - Oct 1 2017

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Experimental Arthritis
Macrophage Activation
Rheumatoid Arthritis
Antibodies
Macrophages
Phosphatidylinositol 3-Kinases
Proteins
Arthritis
Synovial Fluid
Osteoarthritis
Down-Regulation
Ankle
Collagen
Injections
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis. / Zhu, Wei; Yu, Jianbo; Qiu, Shou; Liu, Haifeng; Wang, Yan; Xu, Xiaoyan; Shao, Lili; Zhu, Lingling; Jiao, Yan; Liu, Fan; Zhu, Xiaodong.

In: International Immunopharmacology, Vol. 51, 01.10.2017, p. 40-46.

Research output: Contribution to journalArticle

Zhu, Wei ; Yu, Jianbo ; Qiu, Shou ; Liu, Haifeng ; Wang, Yan ; Xu, Xiaoyan ; Shao, Lili ; Zhu, Lingling ; Jiao, Yan ; Liu, Fan ; Zhu, Xiaodong. / MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis. In: International Immunopharmacology. 2017 ; Vol. 51. pp. 40-46.
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abstract = "Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160 IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.",
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AU - Xu, Xiaoyan

AU - Shao, Lili

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AU - Zhu, Xiaodong

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