International dental journal · 2025
Targeting MSR1 to Facilitate Efferocytosis: A Novel Strategy for Immune Homeostasis Regulation in Irreversible Pulpitis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Liu Sitong, Dang Longrui, Guo Xiaolan, Wu Kailun, Qu Xiaofei, Xu Jing, Wu Buling, Chen Zhao
Аннотация
AIM: To investigate the role of macrophage-mediated efferocytosis in resolution of inflammation during irreversible pulpitis, with a focus on the functional relevance of macrophage scavenger receptor 1 (MSR1).
METHODS: Whole-transcriptome sequencing was performed on pulp tissue from 3 healthy individuals and 3 with pulpitis, integrated with Gene Expression Omnibus (GEO) datasets (GSE77459, GSE92681; total n = 30). After batch correction, differentially expressed genes (DEGs) were identified (|Fold Change|>1.5, P < .05) and analyzed by Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, CIBERSORT immune cell deconvolution, and machine learning. Efferocytosis activity was validated by immunofluorescence, Quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot (WB). MSR1 was selected for in vivo validation via small interfering RNA (siRNA) knockdown in a rat pulpitis model.
RESULTS: A total of 467 differentially expressed genes were identified, which were enriched in immune response and phagosome-related pathways. Macrophage infiltration was significantly increased in pulpitis tissues, accompanied by upregulation of efferocytosis markers. Immunofluorescence showed that MER proto-oncogene tyrosine kinase (MERTK)-positive macrophages in human inflammatory dental pulp could phagocytize apoptotic cells positive for caspase 3 (CASP3) and poly(ADP-ribose) polymerase (PARP). MSR1 is regarded as a key regulatory factor. Knockdown of Msr1 in rats can impair the clearance of apoptotic cells, reduce the expression of Mertk, and aggravate inflammation.
CONCLUSION: MSR1 maintains immune homeostasis in the dental pulp by promoting macrophage efferocytosis, providing a theoretical basis for targeted vital pulp therapy.
METHODS: Whole-transcriptome sequencing was performed on pulp tissue from 3 healthy individuals and 3 with pulpitis, integrated with Gene Expression Omnibus (GEO) datasets (GSE77459, GSE92681; total n = 30). After batch correction, differentially expressed genes (DEGs) were identified (|Fold Change|>1.5, P < .05) and analyzed by Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, CIBERSORT immune cell deconvolution, and machine learning. Efferocytosis activity was validated by immunofluorescence, Quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot (WB). MSR1 was selected for in vivo validation via small interfering RNA (siRNA) knockdown in a rat pulpitis model.
RESULTS: A total of 467 differentially expressed genes were identified, which were enriched in immune response and phagosome-related pathways. Macrophage infiltration was significantly increased in pulpitis tissues, accompanied by upregulation of efferocytosis markers. Immunofluorescence showed that MER proto-oncogene tyrosine kinase (MERTK)-positive macrophages in human inflammatory dental pulp could phagocytize apoptotic cells positive for caspase 3 (CASP3) and poly(ADP-ribose) polymerase (PARP). MSR1 is regarded as a key regulatory factor. Knockdown of Msr1 in rats can impair the clearance of apoptotic cells, reduce the expression of Mertk, and aggravate inflammation.
CONCLUSION: MSR1 maintains immune homeostasis in the dental pulp by promoting macrophage efferocytosis, providing a theoretical basis for targeted vital pulp therapy.