Journal: Journal of Translational Medicine

Article Title: PPM1A dysfunction aggravates DPN pathology through NF-κB/NLRP3/p-tau axis involving Schwann cell/DRG neuron crosstalk

doi: 10.1186/s12967-026-07678-1

Figure Lengend Snippet: MF targeted PPM1A to repress NLRP3 inflammasome activation. (A , C) Western Blot and its (B , D) quantitative analysis results revealed that the protein levels of NLRP3, p-NF-κB, Casp1 p20, ASC, IL-1β, and TNF-α were increased ( n = 3, biological replicates). (E) The results of WB and its (F) quantitative analysis revealed that MF lost such suppressive effects in the AAV-PPM1A injected STZ mice (STZ + AAV-PPM1A) ( n = 3, biological replicates). (G , I) Immunofluorescence assay results indicated that MF (1.5, 2.5 mg/kg/d) suppressed the levels of NLRP3, ASC in the SN tissues of DPN mice, but (K) lost such suppressive effects in the AAV-PPM1A injected STZ mice (STZ + AAV-PPM1A). (H , J , L) Quantification for (G , I , K) . ( n = 4, biological replicates). (M) Western Blot and its (N) quantification results showed the proteins levels of p-SMAD3, p-NF-κB, NLRP3, PPM1A and SMAD3 treated without HG or with HG, HG + MF, si PPM1A, HG + si PPM1A or HG + si PPM1A + MF in RSC96 cells ( n = 3). (O) qPCR results indicated that pyrrolidyl dithiocarbamate (PDTC) deprived MF of its suppressive capability against IL-1β and NLRP3 in the LPS/ATP-treated RSC96 cells ( n = 3). (P) Western blot with (Q) quantification results showed that PDTC deprived MF of its suppressive capability against p-NF-κB and NLRP3 in the LPS/ATP-treated RSC96 cells ( n = 3). (R) Western blot results showed that MF suppressed the protein levels of NLRP3 and p-NF-κB of HSCs isolated from human SN tissues. (S) Quantification of (R) . (T) Immunofluorescence results showed that MF inhibited the protein expressions of NLRP3 and ASC. (U) Quantification of (T) . Scale bar: 25 μm. Student’s t-test for two-groups: * for P value less than 0.05; ** for P value less than 0.01; *** for P value less than 0.001. One-way ANOVA with Tukey’s test for multi-groups: # for P value less than 0.05; ## for P value less than 0.01; ### for P value less than 0.001

Article Snippet: Pyrrolidine dithiocarbamate ammonium (PDTC), an NF-κB inhibitor, was sourced from MedChemExpress.

Techniques: Activation Assay, Western Blot, Injection, Immunofluorescence, Isolation