ABSTRACT
This study was aimed to reveal the role of ferroptosis in tuberculosis infection. To elucidate the ferroptosis-related DEGs, GEO datasets associated with tuberculosis infection were downloaded. The two external validation GEO datasets were exploited for subsequent verification of the ferroptosis-related DEGs. We further evaluated the correlation among the ferroptosis-related DEGs, therapeutic effects, and drug resistance. Finally, we tried to reveal the engagement of the ferroptosis-related DEGs in bone destruction during TB infection. The present study identified SOCS1 as the only ferroptosis-related DEGs. Compared to the non-TB patients, up-regulation of SOCS1 was evident in the TB patients. After receiving standard anti-TB treatment, significant down-regulation of SOCS1 confirmed its acceptance as the marker for therapeutic efficacy. The involvement of SOCS1 has also been suggested in the regulation of the micro immune environment in TB. Furthermore, SOCS1 might play an important role in causing bone destruction during TB infection. FRGs-SOCS1 may be the key gene involved in the pathogenesis and progression of TB infection.
Subject(s)
Suppressor of Cytokine Signaling 1 Protein/analysis , Tuberculosis/diagnosis , Analysis of Variance , Area Under Curve , Biomarkers/analysis , Biomarkers/blood , Ferroptosis/genetics , Humans , Macrophage Activation , ROC Curve , Statistics, Nonparametric , Suppressor of Cytokine Signaling 1 Protein/blood , Suppressor of Cytokine Signaling 1 Protein/genetics , Tuberculosis/geneticsABSTRACT
This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1) expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline). Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis), bone loss (macroscopic analysis), gene expression (qRT-PCR), and protein expression/activation (Western blotting). The severity of inflammation and bone loss associated with LPS-induced periodontitis increased from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05) increases in SOCS1, RANKL, OPG, and IFN-γ gene expression were observed in the experimental group versus the control group at day 15. SOCS1 protein expression and STAT1 and NF-κB activation were increased throughout the 30-day experimental period. Gingival tissues affected by experimental periodontitis express SOCS1, indicating that this protein may potentially downregulate signaling events involved in inflammatory reactions and bone loss and thus may play a relevant role in the development and progression of periodontal disease.
Subject(s)
Alveolar Bone Loss/pathology , Periodontitis/pathology , Suppressor of Cytokine Signaling 1 Protein/analysis , Alveolar Bone Loss/etiology , Alveolar Bone Loss/metabolism , Animals , Blotting, Western , Immunohistochemistry , Interferon-gamma/analysis , Lipopolysaccharides , Male , NF-kappa B/analysis , Periodontitis/etiology , Periodontitis/metabolism , RANK Ligand/analysis , Random Allocation , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , STAT1 Transcription Factor/analysis , Time FactorsABSTRACT
The importance of signal transducer and activator of transcription 3 (STAT3) signaling in the growth and survival of glioblastoma cells has been well documented, while the reasons leading to STAT3 activation remains to be elucidated. Suppressors of cytokine signaling (SOCS) 1 and SOCS3, SH2 domaincontaining phosphatase (SHP2) and protein inhibitors of activated STAT3 (PIAS3) are known to inhibit STAT3 signal transduction, while their expression statuses in the four grades of astrocytomas and relevance with STAT3 activation remain to be described. The present study aimed to address these issues by tissue microarraybased immunohistochemical profiling the expression levels of phosphorylated (p)STAT3, SOCS1, SOCS3, PIAS3 and pSHP2. The results revealed that pSTAT3 nuclear translocation was rarely observed in noncancerous brain tissues and its frequencies were increased in a tumor gradeassociated manner (65.2, 77.1, 81.8 and 85.7% for grade IIV, respectively). PIAS3, pSHP2, SOCS1 and SOCS3 were expressed in higher levels (++ and +++) in 63.6, 90, 87.5 and 81.8% of tumor surrounding brain tissues, which reduced to 13.1, 47.8, 33.3 and 50% in grade I, 11.4, 65.7, 58.3 and 77.1% in grade II, 9.1, 63.6, 38.1 and 31.8% in grade III and 7.1, 66.7, 30.8 and 7.1% in grade IV astrocytomas. The above results revealed that although the expression levels of SOCS1, SOCS3 and, in particular, pSHP2, tend to decrease in the four types of astrocytomas, PIAS3 downregulation is more negatively correlated with STAT3 activation in the stepwise progress of astrocytomas and would indicate an unfavorable outcome.
Subject(s)
Astrocytoma/pathology , Brain Neoplasms/pathology , Brain/pathology , Molecular Chaperones/analysis , Protein Inhibitors of Activated STAT/analysis , Protein Tyrosine Phosphatase, Non-Receptor Type 11/analysis , STAT3 Transcription Factor/analysis , Suppressor of Cytokine Signaling 1 Protein/analysis , Suppressor of Cytokine Signaling 3 Protein/analysis , Astrocytoma/metabolism , Brain/metabolism , Brain Neoplasms/metabolism , Glioblastoma/pathology , Humans , Immunohistochemistry , Molecular Chaperones/metabolism , Protein Inhibitors of Activated STAT/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , STAT3 Transcription Factor/metabolism , Suppressor of Cytokine Signaling 1 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/metabolismABSTRACT
Abstract This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1) expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline). Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis), bone loss (macroscopic analysis), gene expression (qRT-PCR), and protein expression/activation (Western blotting). The severity of inflammation and bone loss associated with LPS-induced periodontitis increased from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05) increases in SOCS1, RANKL, OPG, and IFN-γ gene expression were observed in the experimental group versus the control group at day 15. SOCS1 protein expression and STAT1 and NF-κB activation were increased throughout the 30-day experimental period. Gingival tissues affected by experimental periodontitis express SOCS1, indicating that this protein may potentially downregulate signaling events involved in inflammatory reactions and bone loss and thus may play a relevant role in the development and progression of periodontal disease.