한빛사논문
건양대학교
Roza Khalmuratova 1,2, Jae-Sung Ryu 3,4, Ji Hyeon Hwang 3,4, Yi Sook Kim 1,5,6,7, Suha Lim 1,5, Ji-Hun Mo 8,9, Jong-Yeup Kim 3,4, Hyun-Woo Shin 1,2,5,6,7,10
1Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
2Ischemic Hypoxia Disease Institute, Seoul National University Medical Research Center, Seoul, Korea.
3Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea.
4Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Korea.
5Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
6Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea.
7Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
8Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea.
9Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Korea.
10Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
Roza Khalmuratova and Jae-Sung Ryu equally contributed to this work as the first authors.
Corresponding Authors: Jong-Yeup Kim, Hyun-Woo Shin
Abstract
Background: Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP).
Methods: Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model.
Results: NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1β, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells.
Conclusions: These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.
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