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. 2025 Apr 17;9(4):e70131.
doi: 10.1002/hem3.70131. eCollection 2025 Apr.

Spironolactone inhibits the NLRP1 inflammasome and alleviates defective erythropoiesis in Diamond-Blackfan anemia

Lola Rodríguez-Ruiz  1   2   3 , Juan M Lozano-Gil  1   2   3 , María Ocaña-Esparza  1   2 , Ana M Conesa-Hernández  1   2 , Ana B Pérez-Oliva  2 , José L Fuster  2   4 , Andrés Jérez  2   3   5 , Laura Murillo-Sanjuán  3   6 , Cristina Díaz-de-Heredia  3   6 , Guzmán López-de-Hontanar  3   7 , Julián Sevilla  3   7 , Diana García-Moreno  2   3 , María L Cayuela  2   3   8 , Alicia Martínez-López  2   3 , Sylwia D Tyrkalska  2   3 , Victoriano Mulero  1   2   3
Affiliations

Spironolactone inhibits the NLRP1 inflammasome and alleviates defective erythropoiesis in Diamond-Blackfan anemia

Lola Rodríguez-Ruiz et al. Hemasphere. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Spironolactone regulates hematopoiesis in zebrafish. Experimental design (A), survival (B), caspase‐1 activity (C) and number of neutrophils (D, J), erythrocytes (F, K) and HSPCs (H) of 2 day‐postfertilization (dpf) Tg(lyz:dsRED), Tg(gata1a:dsRED) and Tg(cd41:eGFP) larvae, respectively, injected with RNAs encoding wild type (WT) or catalytic‐dead (C270A) Caspa at the one‐cell stage and treated from 1 to 2 dpf by bath immersion with either 10 µM spironolactone or DMSO. Representative images of neutrophils (E), erythrocytes (G) and HSPCs (I) (labelled with arrowheads) are also shown. Each dot represents one individual and the mean ± SEM for each group is also shown. p values were calculated using Log‐Rank test (B), Student's t‐test (C, D, F, H) and ANOVA followed by Tukey multiple comparison test (J, K). n.s., non‐significant; CHT, caudal hematopoietic tissue; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.
Figure 2
Figure 2
Spironolactone alleviates erythropoiesis defects in zebrafish and human DBA models, as well as in HSPCs from DBA patients. (A) Hemoglobin staining in 2 dpf crRNA rps19/Cas9 complexes‐injected larvae treated from 1 to 2 dpf by bath immersion with 10 μM of spironolactone or DMSO. (B) BMMCs and PBMCs from DBA patients were incubated for 2 weeks in human methylcellulose complete medium at 37°C in the presence or absence of 10 µM spironolactone, and BFU‐E and CFU‐GM colonies counted using standard morphological criteria. Note that BMMCs were used from patient 1 and PBMC from the rest of patients. Each dot represents one individual and the means ± SEM for each group is also shown. (C) Primary human CD34+/CD133+ HSPCs from human cord blood were edited with either AAVS1 or RPS19 gRNA/Cas9 complexes and differentiated for 13 days with EPO in the presence of either DMSO or 10 µM spironolactone. Cells were stained with anti‐CD235A‐APC (Glycophorin A) and anti‐CD71‐FITC (Transferrin Receptor) and erythroid differentiation was then analyzed by flow cytometry. The differentiation score (ratio between CD71+/CD235A+ (intermediate erythroid progenitors and reticulocytes) and CD71+/CD235A− (early erythroid progenitors), and the percentage of CD235A+/CD71high (erythroblasts) and CD235A+/CD71low (reticulocytes) are shown. p values were calculated using Student´s t‐test (B) and ANOVA followed by Tukey multiple comparison test (A, C). ns, non‐significant; ROI, region of interest; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.
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References

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