IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

The nasal polyps (NPs) microenvironment comprises multiple cell types, including mesenchymal stromal cells (MSCs). Insulin-like growth factor binding protein 2 (IGFBP2) plays crucial roles in cell proliferation, differentiation and more. However, the role of NPs-derived MSCs (PO-MSCs) and IGFBP2 in NPs pathogenesis remains poorly defined. Herein, primary human nasal epithelial cells (pHNECs) and MSCs were extracted and cultured. Extracellular vesicles (EVs) and soluble proteins were isolated to investigate the role of PO-MSCs on epithelial-mesenchymal transition (EMT) and epithelial barrier function in NPs. Our data showed that IGFBP2, but not EVs from PO-MSCs (PO-MSCs-EVs), exhibited a crucial role in EMT and barrier destruction. Moreover, focal adhesion kinase (FAK) signaling pathway is necessary for IGFBP2 to exert its functions in human and mice nasal epithelial mucosa. Altogether, these findings may improve the current understanding of the role of PO-MSCs in NPs microenvironment and ultimately contribute to the prevention and treatment of NPs.

Automated summary

This study reveals the important role of IGFBP2 in the pathogenesis of nasal polyps. Researchers extracted and cultured nasal epithelial cells and MSCs, isolated extracellular vesicles and soluble proteins to investigate the impact of PO-MSCs on epithelial-mesenchymal transition and epithelial barrier function. The results show that IGFBP2 plays a crucial role in EMT and barrier destruction, while extracellular vesicles from PO-MSCs do not. Furthermore, the FAK signaling pathway is necessary for IGFBP2 to exert its functions in nasal epithelial mucosa. Overall, these findings contribute to a better understanding of the role of PO-MSCs in the microenvironment of nasal polyps and may contribute to their prevention and treatment.