Fig. 4: Piezo1 dependent decidual mechanoregulation drives IL-8/G-CSF production.
From: Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum
A Immunohistochemistry images of RelA expression in decidual fibroblasts from PAS patient; Quantification showing distance from scar for dESFs classified according to RelA localization; n = 104 and 253 cells. p = 0.002. B Heatmap showing tpm values of genes encoding mechanosensitive ion channels in dESFs on Physio or Scar; n = 3 biological replicates. C ANSIA analysis of primary EVTs spheroids invasion into scrambled and PIEZO1KD dESFs; n = 10 and 13 spheroids. p = 0.0099. The scrambled control is shared with Fig. 2F since these conditions are studied in the same round of experiment. D Schematic showing HTR8 spheroids invasion into wildtype and gene edited dESFs embedded in Matrigel plugs in mouse. E Invasion area of EVT spheroids in Matrigel plugs containing scrambled and PIEZO1KD dESFs. n = 21 and 15 spheroids. p = 0.004. F Snapshot and calcium transients of dESFs transduced with GCamP6f on Physio and Scar. G Ca2+ peak/basal ratio and transient events (H) in dESFs on Physio and Scar. and n = 44 and 92 cells (G); n = 9 and 25 cells (H) p = 0.03 (G) and 0.002 (H). I Images of dESFs loaded with Fluo4-AM treated with DMSO or Yoda1; Graph showing Ca2+ peak/basal levels. n = 20 cells. J Ca2+ dynamics in scrambled and PIEZO1KD dESFs. n = 48 and 32 cells. K Immunoblots showing abundance of RelA, and phosphorylated RelA in dESFs treated with GsMTx-4, or Yoda1, and in PIEZO1KD dESFs. n = 2 biologically independent experiments. L ELISA measurement of IL-8 and G-CSF concentration in supernatant of dESFs treated with Yoda1 or GsMTx-4. n = 3 biological replicates. p = 4 × 10−6, 0.0005, 0.005, and 0.0009. M Concentration of IL-8 and G-CSF in supernatant of scrambled and PIEZO1KD dESFs. n = 3 biological replicates. p = 0.003 and 0.004. N Immunohistochemistry images and graph showing Piezo1 expression in decidual fibroblasts with cytoplasmic or nuclear RelA localization in PAS patients. n = 42 and 66. p = 2 × 10−7. Data in all bar graphs are showing as mean ± s.d.; statistical significance are determined by unpaired two-tailed t-test (*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001). Source data are provided as a Source Data file. Figure 4D created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).
