Maginnis, M. S. | bioRxiv Science

bioRxiv2025

Glucocorticoid and Mineralocorticoid Receptors Jointly Promote Vascular Development in Kidney Organoids

To examine the co-development of vasculature and renal epithelial tissue, we employed a human pluripotent stem cell-derived kidney organoid system. We found that cooperative signaling through the glucocorticoid receptor and mineralocorticoid receptor via hydrocortisone enabled rich endothelial cell differentiation and vessel formation. Bulk RNA sequencing analysis revealed that hydrocortisone perturbs an angiogenic transcriptional program early in development and promotes instead a pro-endothelial survival transcriptional program, with upregulation of angiopoietin 1 at both the mRNA and protein level. Additionally, we saw that hydrocortisone does not seem to significantly affect gene expression of canonical nephrogenic genes compared to our controls, suggesting its effect is largely restricted to endothelial cell differentiation. Our results show that kidney organoids offer a unique platform to study developmental signals that drive endothelial cell differentiation and vessel formation.

developmental biology↗

bioRxiv2024

Antimicrobial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase

Cetylpyridinium chloride (CPC) is a quaternary ammonium antimicrobial used in numerous personal care products, human food, cosmetic products, and cleaning solutions. Yet, there is minimal published data on CPC effects on eukaryotes, immune signaling, and human health. Previously, we showed that low-micromolar CPC inhibits rat mast cell function by inhibiting antigen (Ag)-stimulated Ca2+ mobilization, microtubule polymerization, and degranulation. In this study, we extend the findings to human mast cells (LAD2) and present data indicating that CPCs mechanism of action centers on its positively-charged quaternary nitrogen in its pyridinium headgroup. CPCs inhibitory effect is independent of signaling platform receptor architecture. Tyrosine phosphorylation events are a trigger of Ca2+ mobilization necessary for degranulation. CPC inhibits global tyrosine phosphorylation in Ag-stimulated mast cells. Specifically, CPC inhibits tyrosine phosphorylation of specific key players Syk kinase and LAT, a substrate of Syk. In contrast, CPC does not affect Lyn kinase phosphorylation. Thus, CPCs root mechanism is electrostatic disruption of particular tyrosine phosphorylation events essential for signaling. This work outlines the biochemical mechanisms underlying the effects of CPC on immune signaling and allows the prediction of CPC effects on cell types, like T cells, that share similar signaling elements.

pharmacology and toxicology↗