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Metformin Inhibits Transforming Growth Factor β-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids

Authors
 Hong Bae Jeon  ;  Hyun Roh  ;  Hyo Min Ahn  ;  Ju Hee Lee  ;  Chae Ok Yun  ;  Tai Suk Roh  ;  Won Jai Lee 
Citation
 ANNALS OF PLASTIC SURGERY, Vol.86(4) : 406-411, 2021-04 
Journal Title
 ANNALS OF PLASTIC SURGERY 
ISSN
 0148-7043 
Issue Date
2021-04
MeSH
Cells, Cultured ; Fibroblasts / pathology ; Fibrosis ; Humans ; Keloid* / drug therapy ; Keloid* / pathology ; Metformin* / pharmacology ; Transforming Growth Factor beta ; Transforming Growth Factor beta1
Abstract
Accumulation of excessive extracellular matrix (ECM) and aberrant transforming growth factor β (TGF-β) signaling pathway function can be potential therapeutic targets for keloid treatment. In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-β signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids. Human dermal fibroblasts were stimulated with TGF-β (10 ng/mL) and treated with metformin (10 mM). The mRNA and protein expression of ECM components were evaluated by quantitative polymerase chain reaction, western blot, and immunofluorescence assay. In addition, we immunohistochemically examined the expression levels of ECM proteins in keloid spheroids. After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased. In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM). Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids. These findings indicated that metformin inhibits the expression of ECM components in TGF-β-stimulated HDFs and keloid spheroids. Therefore, we suggest the potential of metformin as an effective agent for the treatment of keloids.
Full Text
https://journals.lww.com/annalsplasticsurgery/Fulltext/2021/04000/Metformin_Inhibits_Transforming_Growth_Factor.9.aspx
DOI
10.1097/SAP.0000000000002574
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Tai Suk(노태석) ORCID logo https://orcid.org/0000-0001-8681-159X
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182891
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