Harnessing noncoding RNA‐based macrophage polarization: Emerging therapeutic opportunities for fibrosis

Zhou, Dexi; Wu, Yilai; Wang, Sheng; Li, Jun; Luan, Jiajie

doi:10.1002/iid3.341

Cited by 6 publications

(3 citation statements)

References 97 publications

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“…The functions of circRNAs are different according to their localization in cells [30,31]. Most circRNAs molecules are localized in the cytoplasm and exert effects by RNA-RNA interactions including sponging with miRNAs and antagonizing their posttranscriptional regulatory effects on the downstream mRNAs [32,33].…”

Section: Discussionmentioning

confidence: 99%

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Yang

et al. 2023

Mediators of Inflammation

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Accumulating studies have implicated that circular RNAs (circRNAs) play vital roles in the pathogenesis of rheumatoid arthritis (RA). Dysregulation of macrophage polarization leads to immune homeostatic imbalance in RA. However, the altering effects and mechanisms of circRNAs on macrophages polarization and immune homeostatic balance remain largely unclear. We aimed to investigate the potential role of circRNA_17725 in RA. The high-throughput sequence was performed to identify the dysregulated circRNAs in RA. We confirmed the data by CCK-8, EdU, and Annexin V/PI staining to elucidate the proliferation and apoptosis. The expressions of M1/M2-associated markers were confirmed using real-time PCR and flow cytometry analysis. Luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) were used to demonstrate the underlying mechanism of circRNA_17725. The altering effect of circRNA_17725 on macrophages in vivo was evaluated using collagen-induced arthritis (CIA) mouse model. circRNA_17725 was demonstrated to be downregulated in peripheral blood mononuclear cells and CD14+ monocytes from RA cases in contrast to healthy controls. The negative association between circRNA_17725 and the disease activity indexes (CRP, ESR, and DAS28) was observed, suggesting a vital role of circRNA_17725 in RA disease activity. Besides, after a coexpression analysis based on high-input sequencing and the bioinformatics analysis in MiRanda and TargetScan databases, a circRNA_17725-miR-4668-5p-FAM46C competing endogenous RNA (ceRNA) network was hypothesized. A series of cytology experiments in vitro have implicated that circRNA_17725 could inhibit the proliferation but enhance the apoptosis of macrophages. Decreased expression of TNF-α, IL-1β, and MMP-9 were observed in the supernatant of circRNA_17725-overexpressed Raw264.7 macrophages, implicating the inhibitory effect of circRNA_17725 on macrophage inflammatory mediators. Furthermore, circRNA_17725 could promote macrophage polarization towards M2 by targeting miR-4668-5p/FAM46C as a miRNA sponge. Additionally, circRNA_17725-overexpressed macrophages alleviated arthritis and protected against joint injuries and bone destruction by inducing macrophage polarization towards M2 in collagen-induced arthritis (CIA) mice. This study has suggested that circRNA_17725 regulated macrophage proliferation, apoptosis, inflammation, and polarization by sponging miR-4668-5p and upregulating FAM46C in RA.

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Section: Discussionmentioning

confidence: 99%

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Yang

et al. 2023

Mediators of Inflammation

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“…Circular RNAs, a novel class of endogenous non coding RNAs, are widely expressed in mammals. By regulating macrophage polarization, circRNA plays a key role in many diseases, such as tumor [ 24 ], type 1 diabetes mellitus (T1DM) [ 25 ], and fibrosis [ 26 ]. Hsa_circ_0005567 is a new osteoarthritis-related circRNA [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0005567 overexpression promotes M2 type macrophage polarization through miR-492/SOCS2 axis to inhibit osteoarthritis progression

et al. 2021

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Synovial macrophage polarization is essential for osteoarthritis (OA) development. Our study aims to investigate the underlying function and the molecular mechanisms of hsa_circ_0005567 in macrophage polarization. Circular RNA (CircRNA), microRNA (miRNA), and mRNA expression levels were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RNA pull down, luciferase reporter were employed to test the interaction between miR-492 and hsa_circ_0005567/suppressors of cytokine signaling 2 (SOCS2). Ectopic overexpression was used to evaluate the function of hsa_circ_0005567. The supernatant of THP-1 cells was used to incubate chondrocytes. Cell Counting Kit-8 (CCK-8) and flow cytometry were conducted to determine cell viability, proportion of M1 or M2 macrophages and apoptotic rate. The results showed that the hsa_circ_0005567 expression level was downregulated in the synovial tissues of osteoarthritis patients. Overexpression of hsa_circ_0005567 inhibited M1 macrophage polarization, and promoted M2 macrophage polarization. Hsa_circ_0005567 was proved to be a molecular sponge for miR-492, and SOCS2 was verified as the target of miR-492. MiR-492 mimic could reverse the effect of hsa_circ_0005567 overexpression on macrophage polarization. Besides, the supernatant from LPS-treated THP-1 macrophage significantly decreased chondrocytes cell viability and increased cell apoptosis ratio, which was reversed by hsa_circ_0005567 overexpression. In conclusion, hsa_circ_0005567 overexpression promoted M2 macrophage polarization through miR-492/SOCS2 axis to reduced chondrocyte apoptosis, which could inhibit osteoarthritis progression.

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“…In another study, miR-140 was reported with a key protective role against RILF by inhibiting myofibroblast differentiation and inflammation, and its loss was suggested to induce lung fibrosis through reprogramming fibroblasts and M2 macrophages ( 76 ). The role of non-coding RNAs in modulating macrophage phenotypic plasticity and functional heterogeneity among different fibrotic diseases has been recently reviewed ( 77 ). These reports further highlight the plausible role of macrophage-derived microRNAs in PF.…”

Section: Microrna-based Regulation Of Macrophage Polarization In Immune Response Inflammation and Fibrosismentioning

confidence: 99%

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

2021

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This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

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Harnessing noncoding RNA‐based macrophage polarization: Emerging therapeutic opportunities for fibrosis

Cited by 6 publications

References 97 publications

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Circular RNA hsa_circ_0005567 overexpression promotes M2 type macrophage polarization through miR-492/SOCS2 axis to inhibit osteoarthritis progression

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

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