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Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-b...

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Autores principales: Wang, Lianhao, Zhong, Nian-Nian, Wang, Xiaofeng, Peng, Boyuan, Chen, Zhuo, Wei, Lili, Li, Bo, Li, Yuhong, Cheng, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671059/
https://www.ncbi.nlm.nih.gov/pubmed/38003450
http://dx.doi.org/10.3390/ijms242216260
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author Wang, Lianhao
Zhong, Nian-Nian
Wang, Xiaofeng
Peng, Boyuan
Chen, Zhuo
Wei, Lili
Li, Bo
Li, Yuhong
Cheng, Yong
author_facet Wang, Lianhao
Zhong, Nian-Nian
Wang, Xiaofeng
Peng, Boyuan
Chen, Zhuo
Wei, Lili
Li, Bo
Li, Yuhong
Cheng, Yong
author_sort Wang, Lianhao
collection PubMed
description Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-β1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin’s anti-fibrotic properties. Elevated levels of TGF-β1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-β1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.
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spelling pubmed-106710592023-11-13 Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study Wang, Lianhao Zhong, Nian-Nian Wang, Xiaofeng Peng, Boyuan Chen, Zhuo Wei, Lili Li, Bo Li, Yuhong Cheng, Yong Int J Mol Sci Article Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-β1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin’s anti-fibrotic properties. Elevated levels of TGF-β1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-β1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis. MDPI 2023-11-13 /pmc/articles/PMC10671059/ /pubmed/38003450 http://dx.doi.org/10.3390/ijms242216260 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Lianhao
Zhong, Nian-Nian
Wang, Xiaofeng
Peng, Boyuan
Chen, Zhuo
Wei, Lili
Li, Bo
Li, Yuhong
Cheng, Yong
Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title_full Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title_fullStr Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title_full_unstemmed Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title_short Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study
title_sort metformin attenuates tgf-β1-induced fibrosis in salivary gland: a preliminary study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671059/
https://www.ncbi.nlm.nih.gov/pubmed/38003450
http://dx.doi.org/10.3390/ijms242216260
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