Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression
Abstract Background Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. Results High dose...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-11-01
|
Series: | BMC Molecular and Cell Biology |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12860-020-00325-7 |
id |
doaj-277251cf7cbb4c51a453425b38d880a9 |
---|---|
record_format |
Article |
spelling |
doaj-277251cf7cbb4c51a453425b38d880a92020-11-25T04:07:19ZengBMCBMC Molecular and Cell Biology2661-88502020-11-0121111010.1186/s12860-020-00325-7Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expressionQiang Chen0Jiuyang Jiao1Youyuan Wang2Zhihui Mai3Jing Ren4Sijie He5Xiaolan Li6Zheng Chen7Department of Stomatology, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Oral & Maxillofacial Surgery & Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Oral & Maxillofacial Surgery & Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Stomatology, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Stomatology, the Third Affiliated Hospital of Sun Yat-sen UniversityThe fourth people’s hospital of Nanhai district of Foshan cityGuanghua School of stomatology & hospital of stomatology, Guangdong province key laboratory of stomatology, Sun Yat-sen UniversityDepartment of Stomatology, the Third Affiliated Hospital of Sun Yat-sen UniversityAbstract Background Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. Results High doses of arecoline (> 32 μg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 μg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation. Conclusions Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.http://link.springer.com/article/10.1186/s12860-020-00325-7ArecolineWnt5aEgr-1FibrosisOral submucous fibroblast |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiang Chen Jiuyang Jiao Youyuan Wang Zhihui Mai Jing Ren Sijie He Xiaolan Li Zheng Chen |
spellingShingle |
Qiang Chen Jiuyang Jiao Youyuan Wang Zhihui Mai Jing Ren Sijie He Xiaolan Li Zheng Chen Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression BMC Molecular and Cell Biology Arecoline Wnt5a Egr-1 Fibrosis Oral submucous fibroblast |
author_facet |
Qiang Chen Jiuyang Jiao Youyuan Wang Zhihui Mai Jing Ren Sijie He Xiaolan Li Zheng Chen |
author_sort |
Qiang Chen |
title |
Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression |
title_short |
Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression |
title_full |
Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression |
title_fullStr |
Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression |
title_full_unstemmed |
Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression |
title_sort |
egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of wnt5a expression |
publisher |
BMC |
series |
BMC Molecular and Cell Biology |
issn |
2661-8850 |
publishDate |
2020-11-01 |
description |
Abstract Background Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. Results High doses of arecoline (> 32 μg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 μg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation. Conclusions Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer. |
topic |
Arecoline Wnt5a Egr-1 Fibrosis Oral submucous fibroblast |
url |
http://link.springer.com/article/10.1186/s12860-020-00325-7 |
work_keys_str_mv |
AT qiangchen egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT jiuyangjiao egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT youyuanwang egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT zhihuimai egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT jingren egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT sijiehe egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT xiaolanli egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression AT zhengchen egr1mediateslowdosearecolineinducedhumanoralmucosafibroblastproliferationviatransactivationofwnt5aexpression |
_version_ |
1724429288604696576 |