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

Bo You; Ting Zhang; Wei Zhang; Yinyin Pei; Danyi Huang; Yun Lei; Shaocong Zhang; Changyu Qiu; Jie Zhang; Zhifeng Gu; Lei Cheng; Jing Chen

doi:10.1016/j.isci.2023.106151

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

iScience. 2023 Feb 7;26(3):106151. doi: 10.1016/j.isci.2023.106151. eCollection 2023 Mar 17.

Authors

Bo You^{1

2}, Ting Zhang^{1

2}, Wei Zhang^{1

2}, Yinyin Pei^{1

2}, Danyi Huang^{1

2}, Yun Lei^{1

2}, Shaocong Zhang^{1

2}, Changyu Qiu^{3

4}, Jie Zhang^{1

2}, Zhifeng Gu⁵, Lei Cheng^{3

4}, Jing Chen^{1

2}

Affiliations

¹ Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
² Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
³ Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
⁴ International Center for Allergy Research, Nanjing Medical University, Nanjing 210029, China.
⁵ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.

Abstract

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.

Keywords: Cell biology; Molecular biology; Stem cells research.