Fig 2: TG2 expression correlates with degraded myelin in active lesions after MS. Active lesions in brain tissues from both RRMS (A–C) and PMS (D–F) showed elevated levels of TG2 (A,C and D,F) respectively. TG2 correlated with levels of degraded myelin surrounding sclerotic plaques of both forms of MS (B,C and E,F, respectively). Inactive lesions from RRMS (G–I) and PMS (J–L) exhibited reduced levels of TG2 and degraded myelin. Quantitative assessment of TG2 levels in sclerotic plaques of both RRMS and PMS brain tissue exhibited significant differences in TG2 expression levels between active and inactive lesions (M). Scale bar = 50 µm. Data were quantified and expressed as value of the mean plus the standard deviation (SD). Statistical significance indicated a * p < 0.05; ** p < 0.01, determined using a 1-way analysis of variance and post hoc Tukey test. Degraded myelin immunoreactivity showed a significant, positive correlation with the extent of TG2 expression in lesioned tissue after both RRMS (N) and PMS (O). The correlation between levels of degraded myelin and TG2 IR in the lesions from all the patients in each of the two forms of MS is shown in (N,O). The p-value determined by linear regression and Pearson correlation coefficient (r) is indicated for each of the analyses.

Fig 3: Regulation of interleukin-1ß (IL-1ß)-induced chemokine expression in gastric cancer cells by TGM2.a Overexpression of TGM2 in MKN-45 cells. The protein expression levels of TGM2 were evaluated by western blotting. b mRNA levels of CCL2 and CXCL10 in IL-1ß (10 ng/mL)-treated MKN-45 cells. The mRNA expression of CCL2 and CXCL10 in TGM2-overexpressing and control cells was measured by real-time PCR at the indicated times. Asterisks indicate statistically significant differences (**P < 0.01; ***P < 0.001) compared to the control cells. c THP-1 macrophage migration induced by conditioned medium from MKN-45 cells. TGM2-overexpressing and control MKN-45 cells were treated with IL-1ß (10 ng/mL), and the chemotactic effect of conditioned medium on THP-1 cells was estimated with a cell migration assay. Migrated cells were lysed and quantified using a fluorescent dye. Asterisks indicate statistically significant differences (***P < 0.001) compared to control cells. d The activity of an NF-?B-responsive element (6 × NF?B) after IL-1ß treatment (10 ng/mL). The activity of the NF-?B-responsive element was estimated using a luciferase reporter assay to assess TGM2-overexpressing and control MKN-45 cells. Asterisks indicate statistically significant differences (***P < 0.001) compared to control cells. e Time-dependent changes in the protein levels of NF-?B after IL-1ß treatment (10 ng/mL). The protein levels of total and phospho-NF-?B (Ser276 and Ser536) in TGM2-overexpressing and control MKN-45 cells were evaluated by western blotting at the indicated times.

Fig 4: Correlations between TGM2 expression and immune cell type-specific gene expression in 80 gastric cancer tissue specimens.Microarray data were downloaded from Gene Expression Omnibus (GEO; GSE27342), and the heatmap represents the matrix of gene expression of TGM2 and 76 immune cell type-specific genes representing 23 cell types, which are shown in colored gene names and bars (right). Each column represents an individual GC sample, and each row denotes a gene. The correlation between TGM2 expression and immune cell type-specific gene expression was estimated by linear regression analysis, and the P-values for genes that were significantly correlated with TGM2 expression are depicted (P < 0.05; red: positive correlation, blue: negative correlation). DCs dendritic cells, aDCs activated DCs, iDCs immature DCs, pDCs plasmacytoid DCs, Tem effector memory T cell, Tfh follicular helper T cell, T?d gamma delta T cell, and Treg regulatory T cell.

Fig 5: Hematoxylin and eosine staining in glioblastoma stem cells (GSC 528 (a) and GSC 157 (b) tumors at day 19 of embryonic development. CE: chorionic epithelium, AE: allantoic epithelium, M: intermediate vascularized mesenchyme, BV: blood vessel, and T: tumor. TGM2 (c: GSC 528; d: GSC 157) and SOX2 (e: GSC 528; f: GSC 157) protein expression in tumor cells; TGM2-positive staining is in red (c). Scale bars are 1 (a,b) and 0.1 mm (c–f).