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Cited by 4Mesenchymal stem cell researchLiver physiology and pathologyTGF-β signaling in diseases

Reduced glutathione enhances adipose tissue‐derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway

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Yu, Shaoxiong, Wang, Yingchao, Shi, Yingjun, Yu, Saihua, Zhao, Bixing, Liao, Naishun, Liu, Xiaolong·2025·Bioengineering & Translational Medicine
DOI 10.1002/btm2.10735PMC PMC11883125
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Abstract

Reduced glutathione (GSH) could reduce oxidative stress to improve adipose tissue‐derived mesenchymal stem cell (ADSC) engraftment efficiency in vivo. However, the underlying mechanisms remain unclear. Our goal is to investigate whether GSH enhances ADSC engraftment through targeting the TGFβ/SMAD3/NOX4 pathway. Liver fibrotic male mice were administrated GSH, setanaxib (STX), and SIS3 during ADSC transplantation. ADSC engraftment efficiency and reactive oxygen species (ROS) level were detected both in vivo and ex vivo. Biochemical analysis was used to analyze the content of superoxide and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in liver tissues. Immunohistochemistry and western blotting were used to examine the protein level of NOX1, NOX2, NOX4, transforming growth factor‐β1 (TGFβ1), SMAD3, and p‐SMAD3 in liver tissues. Additionally, the therapeutic efficacy of the ADSC transplantation was further investigated. We found that GSH significantly improved ADSC engraftment efficiency, which was closely related to the reduced ROS generation in liver tissues. However, the enhanced cell engraftment was abolished after the combined treatment with STX or SIS3. GSH could effectively reduce superoxide and NOXs content, and selectively inhibit NOX4 expression in liver tissues. The co‐localization results showed that GSH could reduce NOX4 expressed in activated hepatic stellate cells. Mechanistically, GSH down‐regulated TGFβ/SMAD3 signaling. More importantly, GSH enhanced the therapeutic efficacy of ADSC therapy in liver fibrotic mice. Taken together, GSH could improve the engraftment efficiency of ADSCs in liver fibrosis by targeting TGFβ1/SMAD3/NOX4 signaling pathway, which provides a new theoretical basis for GSH enhancing ADSC engraftment efficiency in liver diseases.

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Cited by

Sorted by citations

Authors
Yu, S., Wang, Y., Shi, Y., Yu, S., Zhao, B., Liao, N., & Liu, X.
Affiliations
Fujian Medical University (CN)
Corresponding author
  • Liao, Naishun
  • Liu, Xiaolong
ORCID
Venue
Bioengineering & Translational Medicine
Publisher
Wiley
Published
2024-12-10
Volume
10
Issue
2
Pages
e10735-e10735
ISSN
2380-6761 (ISSN-L)
DOI
10.1002/btm2.10735
PMC
PMC11883125
OpenAlex
W4405233712
Cited by
4
References
1
Citations by year
2026: 3 · 2025: 1
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioengineering & Translational Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
reduced glutathione, adipose-derived stem cells, stem cell engraftment, liver fibrosis, NOX4, reactive oxygen species, oxidative stress, hepatic stellate cells, SIS3, stem cell transplantation

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