한빛사논문
- 조회1,833
Jun-Sang Bae1,2,3, Gwanghui Ryu4, Ji Hye Kim1,2, Eun Hee Kim1,2, Yun Hee Rhee1,2,3, Young-Jun Chung1,2,3, Dae Woo Kim5, Suha Lim6,7, Phil-Sang Chung1,2,3, Hyun-Woo Shin6,7,8,9, Ji-Hun Mo1,2,3
1Otorhinolaryngology, Dankook University College of Medicine, Cheonan, South Korea
2Beckman Laser Institute Korea and Medical Laser Research Center, Dankook University College of Medicine, Cheonan, South Korea
3Laser Translational Clinical Trial Center, Dankook University Hospital, Cheonan, South Korea
4Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan, South Korea
5Otorhinolaryngology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea
6Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea
7Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea
8Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
9Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, South Korea
J-SB and GR contributed equally.
Correspondence to Professor Ji-Hun Mo, Professor Hyun-Woo Shin
Abstract
Background
Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood.
Objective
We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues.
Methods
Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients.
Results
ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear β-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear β-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP.
Conclusion
Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.
논문정보
- Research article
- 2020년 10월 (BRIC 등록일 2020-10-30)
- 국내 연구진
- 의약학 > 약리의학
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