Journal article
Dicer-independent miR-451a is upregulated in periodontitis and potentiates inflammation by impairing macrophage polarization and SOCS activity
Inflammation research, Vol.75(1), 233
10/06/2026
DOI: 10.1007/s00011-026-02381-9
PMID: 42839140
Abstract
Background
Periodontitis (PD) is characterized by localized inflammatory tissue destruction, yet the lesion-associated microRNA (miRNA)networks that regulate host immune responses remain incompletely defined. In this study, we aimed to identify and characterize dysregulated gingivalmiRNAs in PD that modulate inflammatory responses.
Methods
Using a split-mouth design, miRNA expression was profiled in gingival biopsies fromperiodontal lesions and clinically healthy sites. Differentially expressed miRNAs were identified by microarray analysis, and selected candidates werevalidated by RT-qPCR. The responses of candidate miRNAs to periodontal bacterial challenge were evaluated, followed by functional studies ofmacrophage polarization, phagocytosis, inflammatory cytokine production, and target-gene regulation.
Results
Microarray analysis identified 48differentially expressed miRNAs, including several upregulated non-canonical miRNAs. Among these, the Dicer-independent miRNAs miR-451a andmiR-1228 showed dose- and time-dependent induction following periodontal bacterial challenge. miR-451a, but not miR-1228, promoted a pro-inflammatory M1-like macrophage phenotype, characterized by increased HLA-DR and CD32 and reduced CD206 and CD163 expression. miR-451adirectly targeted multiple genes associated with M2 macrophage polarization, and its expression in inflamed gingival tissues inversely correlated with M2markers. miR-451a overexpression also reduced macrophage phagocytosis of E. coli and P. gingivalis while increasing pro-inflammatory cytokineproduction. Mechanistically, miR-451a directly suppressed SOCS3 and SOCS5, key negative regulators of JAK/STAT signaling, in TLR4-stimulated cells.The antagonistic expression patterns of miR-451a, SOCS3, and SOCS5 in PD further supported the functional relevance of this regulatory axis.
Conclusion
miR-451a is a pathogen-responsive, PD-associated miRNA that promotes pro-inflammatory macrophage polarization, impairs bacterialphagocytosis, and amplifies inflammation through suppression of SOCS-mediated immune regulation. These findings identify the miR-451a–SOCS3/SOCS5 axis as a potential mechanism linking bacterial challenge to dysregulated macrophage responses in PD.
Details
- Title: Subtitle
- Dicer-independent miR-451a is upregulated in periodontitis and potentiates inflammation by impairing macrophage polarization and SOCS activity
- Creators
- Raza Ali Naqvi - University of Illinois ChicagoJack Maddalozzo - University of Illinois ChicagoKreena Amin - University of Illinois ChicagoKristelle Capistrano - University of Illinois ChicagoAraceli Valverde - University of Illinois ChicagoRani Rahat - University of Illinois ChicagoHasan Siddiqui - University of Illinois ChicagoWei Li - University of Illinois ChicagoChristine D. Wu - University of Illinois ChicagoShaoping Zhang - University of IowaMary Pettiette - Virginia Commonwealth UniversityAntonio Moretti - University of North Carolina at Chapel HillGatikrushna Singh - University of MinnesotaSalvador Nares - University of Illinois ChicagoAfsar Naqvi - University of Illinois Chicago
- Resource Type
- Journal article
- Publication Details
- Inflammation research, Vol.75(1), 233
- DOI
- 10.1007/s00011-026-02381-9
- PMID
- 42839140
- NLM abbreviation
- Inflamm Res
- ISSN
- 1420-908X
- eISSN
- 1420-908X
- Publisher
- Springer International Publishing
- Grant note
- DE021052; DE027980 / National Institute of Dental and Craniofacial Research (https://doi.org/10.13039/100000072)
- Language
- English
- Date published
- 10/06/2026
- Academic Unit
- Periodontics
- Record Identifier
- 9985241978602771
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