Macrophage pyroptosis, luminal senescence and club cells in 5-ARI-treated prostate hyperplasia
In 5-ARI-exposed prostate tissue, the abstract reports more cleaved-GSDMD⁺ macrophages, higher epithelial p16 and more SCGB1A1⁺ club cells, linked to MIF-CD74 and HMGB1-AGER signaling. [1]
Automatic summary · not editorially reviewed
The key findings
In 5-ARI-exposed prostate tissue, the abstract reports enrichment of cleaved-GSDMD⁺ macrophages, elevated epithelial p16 and expansion of SCGB1A1⁺ club cells. [1]
Blocking MIF-CD74 or HMGB1-AGER attenuated macrophage pyroptosis and luminal senescence, while Notch inhibition only partially reversed epithelial remodeling. [1]
In a castration/testosterone-induced mouse BPH model, 5-ARI treatment amplified pyroptotic macrophages and club programs, whereas Gsdmd deletion blunted pyroptosis and dampened senescence/club states. [1]
The source at a glance
- Study type / format
- Abstract of a study combining spatial and single-cell transcriptomics with functional perturbations and mouse genetics
- Population / context
- Human prostate tissue exposed to 5α-reductase inhibitors and a castration/testosterone-induced mouse BPH model
- Summary based on
- Study abstract
- Original publication
- October 7, 2026
5-ARI-exposed prostate tissue and its cell changes
The abstract describes benign prostatic hyperplasia (BPH) as a common age-associated disease whose prevalence rises with age. Responses to 5α-reductase inhibitors (5-ARIs) vary, and some patients eventually need surgery, but why disease progresses during treatment was unclear. In 5-ARI-exposed tissue, the authors report enrichment of cleaved-GSDMD⁺ macrophages, elevated epithelial p16 expression and expansion of SCGB1A1⁺ club cells. Spatial mapping located macrophage-epithelium hotspots with prominent MIF-CD74 and HMGB1-AGER signaling.
Supporting source [1]
Proposed signaling chain and partial reversals in experiments
The abstract proposes a chain: under 5-ARI pressure, luminal-cell secretomes recruit macrophages via MIF-CD74; pyroptotic macrophages release HMGB1, which activates epithelial AGER and triggers luminal G1 arrest and senescence; this in turn promotes luminal-to-club reprogramming through a partly Notch-associated program. Blocking MIF-CD74 or HMGB1-AGER attenuated macrophage pyroptosis and luminal senescence, while Notch inhibition only partially reversed epithelial remodeling. A 13-gene pyroptosis-macrophage signature (PM-13) is reported to stratify patient responsiveness to 5-ARIs.
Supporting source [1]
Mouse BPH model and candidate targets named in the abstract
In a castration/testosterone-induced mouse BPH model, 5-ARI treatment amplified pyroptotic macrophages and club programs, whereas Gsdmd deletion blunted pyroptosis and dampened senescence and club transcriptional states. The authors nominate MIF-CD74, HMGB1-AGER, Notch and GSDMD as druggable nodes and candidate targets for intervention and patient stratification in BPH under 5-ARI therapy. These are proposed candidates, not established treatments.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. Design details, sample sizes, follow-up and effect sizes are not reported here. The mouse findings are preclinical, and the named targets are proposed candidates, not established treatments. Associations described do not establish causation in patients.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Li Z, Zhang Z, Zhao Q, Zhu Z, Yang K, Meng Y, Zhang Q, Yu W. · europepmc.org · October 7, 2026