Journal: Aging Cell

Article Title: Characterizing the SASP ‐Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types

doi: 10.1111/acel.70673

Figure Lengend Snippet: Analysis of ligands and receptors in senescent and receiving cells. (A) Schematic depicting BulkSignalR pipeline which uses known ligand‐receptor interactions and affected downstream pathways to analyze their activation based on our bulk RNAseq data from DMSO and BrdU treated human cell lines (created with BioRender). (B) Venn diagram showing the number of receptors inferred from BulkSignalR to be activated across each of the five human cell types. Three receptors were identified in common between astrocytes (purple), endothelial cells (pink), and microglia (yellow) which were the cell types shown (Figure ) to be capable of receiving senescence signals and becoming SA β‐gal positive: CXCR7, KREMEN2, and GIPR. Only CXCR7 was expressed in the cell types capable of entering secondary senescence (astrocytes, endothelial cells, microglia) (Figure , Figure ). (C) TPM expression values of CXCR7 , its ligand CXCL12 , and DPP4 which cleaves and inactivates CXCL12 in DMSO (gray) and BrdU (red) treated cell lines ( n = 3 replicates). (D) Schematic of the four selected SASP inhibitors mechanisms of action: Bindarit is a CCL2 synthesis inhibitor which prevents p65 activation of the CCL2 gene at the promoter region, ISO‐1 is a MIF antagonist, ACT‐1004‐1239 is a CXCR7 antagonist, and Sitagliptin inhibits DPP4 preventing its action of cleaving and inactivating CXCL12 (created with BioRender). Data were analyzed by two‐way ANOVA with Tukey's multiple comparisons test (C). All graphs show mean with error bars depicting standard deviation (ns, p > 0.05, ** p < 0.01, *** p < 0.001).

Article Snippet: Treatment with DPP4 inhibitor Sitagliptin (MedChemExpress, Catalog No. HY‐13749) was used to eliminate DPP4‐dependent cleavage and inactivation of CXCL12, which is a ligand of the CXCR7 receptor.

Techniques: Activation Assay, RNA sequencing, Expressing, Standard Deviation

Journal: Journal of Translational Medicine

Article Title: HIF-1α attenuates ferroptosis-associated dermal fibroblast senescence via modulation of NF-κB–DPP4 signaling

doi: 10.1186/s12967-026-08445-y

Figure Lengend Snippet: Hypoxia-mediated elimination of DPP4 protects HDFs from ferroptosis-associated senescence. (A) Human Protein Atlas database analysis of DPP4 expression across 18 skin cell clusters. (B) DPP4 mRNA expression in human skin from suprapubic (non–sun-exposed) and lower leg (sun-exposed) regions (Human Protein Atlas, https://www.proteinatlas.org ). (C) Quantification of DPP4 IHC staining in sun-exposed and non–sun-exposed skin using a normal human skin tissue array (SKN1001). ( n = 8, 76). (D , E) Flow cytometry of young HDFs treated with erastin (10 µM) or RSL3 (200 nM) for 4 h, washed, and cultured under normoxia or hypoxia for 48 h; quantification of DPP4⁺SPiDER-βGal⁺ cells (Q2 region). ( n = 3 each). (F) qRT-PCR quantification of DPP4 mRNA relative to housekeeping controls. ( n = 3 each). (G , H) Young HDFs treated with erastin or RSL3 for 4 h, washed, and subsequently treated with saxagliptin (50 µM) or sitagliptin (50 µM) under normoxia for 48 h; immunoblotting of COL1A1, COL3A1, MMP-1, MMP-3 and p21. ( n = 3 each). (I) Overexpression of HA-DPP4 or empty vector (3 µg/mL) in young and aged HDFs after ferroptosis induction; immunoblotting of DPP4, COL1A1, COL3A1, MMP-1, MMP-3, and p21. ( n = 3 each). Data are presented as mean ± SD. Quantification of the results is shown * P < 0.05, ** P < 0.01, and *** P < 0.001

Article Snippet: Chemical reagents included doxorubicin (HY-15142), DMOG (HY-15893), Erastin (HY-15763), RSL3 (HY-100218 A), Saxagliptin (HY-10285), Sitagliptin (HY-13749), and recombinant human DPP4 (rhDPP4; HY-N0135), all purchased from MedChemExpress (MCE).

Techniques: Expressing, Immunohistochemistry, Flow Cytometry, Cell Culture, Quantitative RT-PCR, Western Blot, Over Expression, Plasmid Preparation