Senescent mast cells contribute to the progression of benign prostatic hyperplasia via SCF/c-KIT mediated endothelial-mesenchymal transition

Jing, Y.; Li, L.; Guo, W.; Cao, T.; Tang, J.; Zhou, D.; Yao, C.; Xu, J.; Liu, Y.; Feng, C.; Shi, Y.; Wang, M.; Chao, W.; Liao, H.; He, J.; Qin, L.; Luan, J.; Wang, X.; Cui, D.; Zhu, Y.; Ruan, Y.; Xia, S.; Han, B.

doi:10.1101/2025.06.02.657200

bioRxiv · 10.1101/2025.06.02.657200

Senescent mast cells contribute to the progression of benign prostatic hyperplasia via SCF/c-KIT mediated endothelial-mesenchymal transition

Jing, Y.·Li, L.·Guo, W.·Cao, T.·Tang, J.·Zhou, D.·Yao, C.·Xu, J.·Liu, Y.·Feng, C.·Shi, Y.·Wang, M.·Chao, W.·Liao, H.·He, J.·Qin, L.·Luan, J.·Wang, X.·Cui, D.·Zhu, Y.·Ruan, Y.·Xia, S.·Han, B.

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Abstract

Benign prostatic hyperplasia (BPH) is a common age-associated urological condition characterized by stromal expansion, but its cellular origins and regulatory mechanisms remain unclear. In this study, we identified endothelial-to-mesenchymal transition (EndMT) as a contributor to stromal cell accumulation in BPH. Using single-cell transcriptomic analysis, endothelial lineage tracing in mice, and validation in human samples, we showed that senescence-associated mast cells increased the expression of vascular endothelial growth factor A (VEGFA) and transforming growth factor-beta 1 (TGF-{beta}1) through the stem cell factor (SCF)/c-KIT-MAPK-JUND signaling pathway, thereby inducing EndMT in endothelial progenitor cells. Stromal fibroblasts express SCF, promoting mast cell activation and establishing a feedback loop that supports continued stromal proliferation. Intriguingly, inhibition of mast cell activation reduces EndMT and attenuates prostate enlargement in vivo. Thus, these findings revealed a senescence-linked immune-stromal interaction in the aging prostate and identify potential targets for therapeutic intervention in BPH.

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Jing, Y., Li, L., Guo, W., Cao, T., Tang, J., Zhou, D., Yao, C., Xu, J., Liu, Y., Feng, C., Shi, Y., Wang, M., Chao, W., Liao, H., He, J., Qin, L., Luan, J., Wang, X., Cui, D., Zhu, Y., Ruan, Y., Xia, S., Han, B.. 2025-06-05. Senescent mast cells contribute to the progression of benign prostatic hyperplasia via SCF/c-KIT mediated endothelial-mesenchymal transition. https://doi.org/10.1101/2025.06.02.657200

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