PMID- 31175668 OWN - NLM STAT- MEDLINE DCOM- 20201120 LR - 20220531 IS - 1365-2842 (Electronic) IS - 0305-182X (Linking) VI - 47 Suppl 1 DP - 2020 Nov TI - TGF-beta1-induced connexin43 promotes scar formation via the Erk/MMP-1/collagen III pathway. PG - 99-106 LID - 10.1111/joor.12829 [doi] AB - Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise, scar tissue forms in the wounded area. Connexins (Cxs) were confirmed to influence scar formation, and Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of Cx43 in scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key proteins in cell signalling pathways (TGF-beta1, Smad2/3, Cx43, Erk1/2 MMP-1 and collagen III). After injury, buccal mucosa wounds healed with no scar, whereas skin wounds healed with an evident scar. Nevertheless, TGF-beta1 expression gradually increased by the 5th day after injury; Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF-beta1 and Cx43 expression in the oral mucosa remained low. The high level of TGF-beta1 increased p-Smad2/3 levels and then induced Cx43, whereas increased expression of Cx43 antagonised the phosphorylation of Erk1/2, a protein downstream of Cx43, which affected MMP-1 synthesis. MMP-1 deficiency led to collagen III accumulation and facilitated scar formation. We demonstrated that TGF-beta1-induced Cx43 promotes scar formation via the Erk/MMP-1/collagen III pathway. CI - (c) 2019 John Wiley & Sons Ltd. FAU - Li, Xiaoyan AU - Li X AUID- ORCID: 0000-0001-7166-0135 AD - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China. FAU - Guo, Lijia AU - Guo L AD - Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China. FAU - Yang, Xiaohui AU - Yang X AD - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China. FAU - Wang, Jingyi AU - Wang J AD - School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Hou, Yanan AU - Hou Y AD - Department of Orthodontics the Third Dental Center, Peking University School of Stomatology, Beijing, China. FAU - Zhu, Siying AU - Zhu S AD - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China. FAU - Du, Juan AU - Du J AD - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China. FAU - Feng, Jie AU - Feng J AD - Department of General Dentistry, School of Stomatology, Capital Medical University, Beijing, China. FAU - Xie, Yongmei AU - Xie Y AD - Department of General Dentistry, School of Stomatology, Capital Medical University, Beijing, China. FAU - Zhuang, Li AU - Zhuang L AD - Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China. FAU - He, Xin AU - He X AD - Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China. FAU - Liu, Yi AU - Liu Y AD - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China. LA - eng GR - 81470751/National Nature Science Foundation of China/ GR - 81600891/National Nature Science Foundation of China/ GR - 7172087/Beijing Natural Science Foundation/ GR - 2016-2-2141/The Capital Health Research and Development of Special/ GR - ZYLX201703/Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support/ GR - 2017A17/Beijing Baiqianwan Talents Project/ GR - DFL20181501/Beijing Municipal Administration of Hospitals' Ascent Plan/ GR - Z16100000516203/Beijing Municipal Science & Technology Commission/ GR - QML20181501/Beijing Municipal Administration of Hospitals' Youth Programme/ GR - Beijing Dongcheng Excellent Talent/ PT - Journal Article DEP - 20191031 PL - England TA - J Oral Rehabil JT - Journal of oral rehabilitation JID - 0433604 RN - 0 (Connexin 43) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Animals MH - Cicatrix MH - Collagen MH - *Connexin 43 MH - Humans MH - Matrix Metalloproteinase 1/genetics MH - Mice MH - Mice, Inbred C57BL MH - *Transforming Growth Factor beta1 OTO - NOTNLM OT - Cx43 OT - TGF-beta1 OT - collagen III OT - scar EDAT- 2019/06/09 06:00 MHDA- 2020/11/21 06:00 CRDT- 2019/06/09 06:00 PHST- 2019/02/24 00:00 [received] PHST- 2019/05/07 00:00 [revised] PHST- 2019/05/26 00:00 [accepted] PHST- 2019/06/09 06:00 [pubmed] PHST- 2020/11/21 06:00 [medline] PHST- 2019/06/09 06:00 [entrez] AID - 10.1111/joor.12829 [doi] PST - ppublish SO - J Oral Rehabil. 2020 Nov;47 Suppl 1:99-106. doi: 10.1111/joor.12829. Epub 2019 Oct 31.