S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling
Epithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue t...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.835888/full |
| _version_ | 1818332735121391616 |
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| author | Ningyue Gong Ningyue Gong Lei Shi Xin Bing Xin Bing Hui Li Houyang Hu Pan Zhang Huiming Yang Na Guo Hongjie Du Ming Xia Ming Xia Chengcheng Liu |
| author_facet | Ningyue Gong Ningyue Gong Lei Shi Xin Bing Xin Bing Hui Li Houyang Hu Pan Zhang Huiming Yang Na Guo Hongjie Du Ming Xia Ming Xia Chengcheng Liu |
| author_sort | Ningyue Gong |
| collection | DOAJ |
| description | Epithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue to identify differentially expressed proteins. Data are available via ProteomeXchange with identifier PXD030884. Specifically, we identified S100 calcium binding protein A4 (S100A4), an effective factor in inflammation-related diseases, and its downstream protein closely related to tissue fibrosis collagen type I alpha 1 chain (COL1A1), which suggested its involvement in nasal mucosal tissue remodeling. In addition, stimulation of human nasal epithelial cells (HNEpCs) with lipopolysaccharide (LPS) mimicked the inflammatory environment of CRS and showed that S100A4 is involved in regulating EMT and thus accelerating tissue remodeling in the nasal mucosa, both in terms of increased cell motility and overexpression of mesenchymal-type proteins. Additionally, we further investigated the regulation mechanism of S100A4 involved in EMT in CRS. Our research results show that in the inflammatory environment of CRS nasal mucosal epithelial cells, TCF-4 will target to bind to S100A4 and regulate its transcription. The transcription of S100A4 in turn affects the execution of the important signaling pathway in EMT, the Wnt/GSK-3β/β-catenin pathway, through the TCF-4/β-catenin complex. In conclusion, this study confirmed that the expression of S100A4 was significantly increased during the progressive EMT process of CRS mucosal epithelial cells, and revealed that the transcriptional regulation of S100A4 plays an important role in the occurrence and development of EMT. This finding will help us to better understand the pathogenesis behind the remodeling in CRS patients, and identify target molecules for the treatment of CRS. |
| first_indexed | 2024-12-13T13:40:28Z |
| format | Article |
| id | doaj.art-6d5dadebe94344d2a7ba4d33b842a560 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T13:40:28Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6d5dadebe94344d2a7ba4d33b842a5602022-12-21T23:43:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011310.3389/fimmu.2022.835888835888S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin SignalingNingyue Gong0Ningyue Gong1Lei Shi2Xin Bing3Xin Bing4Hui Li5Houyang Hu6Pan Zhang7Huiming Yang8Na Guo9Hongjie Du10Ming Xia11Ming Xia12Chengcheng Liu13Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Biotechnology Research and Development, Qilu Pharmaceutical, Co.Ltd, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Otolaryngology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaCentral Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaEpithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue to identify differentially expressed proteins. Data are available via ProteomeXchange with identifier PXD030884. Specifically, we identified S100 calcium binding protein A4 (S100A4), an effective factor in inflammation-related diseases, and its downstream protein closely related to tissue fibrosis collagen type I alpha 1 chain (COL1A1), which suggested its involvement in nasal mucosal tissue remodeling. In addition, stimulation of human nasal epithelial cells (HNEpCs) with lipopolysaccharide (LPS) mimicked the inflammatory environment of CRS and showed that S100A4 is involved in regulating EMT and thus accelerating tissue remodeling in the nasal mucosa, both in terms of increased cell motility and overexpression of mesenchymal-type proteins. Additionally, we further investigated the regulation mechanism of S100A4 involved in EMT in CRS. Our research results show that in the inflammatory environment of CRS nasal mucosal epithelial cells, TCF-4 will target to bind to S100A4 and regulate its transcription. The transcription of S100A4 in turn affects the execution of the important signaling pathway in EMT, the Wnt/GSK-3β/β-catenin pathway, through the TCF-4/β-catenin complex. In conclusion, this study confirmed that the expression of S100A4 was significantly increased during the progressive EMT process of CRS mucosal epithelial cells, and revealed that the transcriptional regulation of S100A4 plays an important role in the occurrence and development of EMT. This finding will help us to better understand the pathogenesis behind the remodeling in CRS patients, and identify target molecules for the treatment of CRS.https://www.frontiersin.org/articles/10.3389/fimmu.2022.835888/fullCRSepigenetic regulationEMTS100A4inflammation |
| spellingShingle | Ningyue Gong Ningyue Gong Lei Shi Xin Bing Xin Bing Hui Li Houyang Hu Pan Zhang Huiming Yang Na Guo Hongjie Du Ming Xia Ming Xia Chengcheng Liu S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling Frontiers in Immunology CRS epigenetic regulation EMT S100A4 inflammation |
| title | S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling |
| title_full | S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling |
| title_fullStr | S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling |
| title_full_unstemmed | S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling |
| title_short | S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling |
| title_sort | s100a4 tcf complex transcription regulation drives epithelial mesenchymal transition in chronic sinusitis through wnt gsk 3β β catenin signaling |
| topic | CRS epigenetic regulation EMT S100A4 inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.835888/full |
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