Reduced glutathione enhances adipose tissue‐derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway DOI Creative Commons
Shaoxiong Yu, Yingchao Wang,

Yingjun Shi

et al.

Bioengineering & Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

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

Language: Английский

Characterization and Proteomic Profiling of Hepatocyte-Like Cells Derived from Human Wharton’s Jelly Mesenchymal Stromal Cells: De Novo Expression of Liver-Specific Enzymes DOI Creative Commons
Melania Lo Iacono, Simona Corrao, Giusi Alberti

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 124 - 124

Published: Jan. 24, 2025

End-stage liver disease (ESLD), affecting millions worldwide, represents a challenging issue for clinical research and global public health. Liver transplantation is the gold standard therapeutic approach but shows some drawbacks. Hepatocyte could be reliable alternative patient treatment. Mesenchymal stromal cells derived from Wharton’s jelly of umbilical cord (WJ-MSCs) can differentiate into hepatocyte-like (HLCs) show immunomodulatory functions. Due to increasing demand fully characterized cell therapy vehicles warranting both safety efficacy treatments, in this work, we extensively WJ-MSCs before after application hepatocyte-directed differentiation protocol. HLCs exhibited morphology resembling that hepatocytes, expressed early late hepatic markers (α-fetoprotein, albumin, CK18, HNF4-α), acquired functions (glycogen synthesis, xenobiotics detoxification), as also revealed by shotgun proteomics approach. maintained same pattern molecule expression mesenchymal markers, other than displaying specific enzymes, suggesting these promising candidates cellular ESLD. Our work shed new light on basic biology HLCs, approaches treat

Language: Английский

Citations

0
Reduced glutathione enhances adipose tissue‐derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway DOI Creative Commons
Shaoxiong Yu, Yingchao Wang,

Yingjun Shi

et al.

Bioengineering & Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

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

Language: Английский

Citations

0