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Cell Communication and Signaling

Cell Communication and Signaling

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Atg5-deficient mesenchymal stem cells protect against non-alcoholic fatty liver by accelerating hepatocyte growth factor secretion

Published:3 December 2024 DOI: 10.1186/s12964-024-01950-x PMID: 39627775
Caifeng Zhang,?Juanjuan Ji,?Xuefang Du,?Lanfang Zhang,?Yaxuan Song,?Yuyu Wang,?Yanan Jiang,?Ke Li,?Tingmin Chang

Abstract

Background/aims: Mesenchymal stem cells (MSCs) have shown promising therapeutic potential in treating liver diseases, such as non-alcoholic fatty liver disease (NAFLD). Genetic modification has been employed to enhance the characteristics of MSCs for more effective disease treatment. Here, we present findings on human adipose-derived MSCs with Atg5 deficiency, investigating their therapeutic impact and the associated mechanisms in NAFLD.

Methods: In vitro, lentiviral transduction was employed to downregulate Atg5 or HGF in human adipose-derived MSCs using short hairpin RNA (shRNA). Subsequently, experiments were conducted to evaluate cell senescence, proliferation, cell cycle, apoptosis, and other pertinent aspects. In vivo, a non-alcoholic fatty liver mouse model was established by feeding them a high-fat diet (HFD), and the effects of MSCs transplantation were assessed through serological, biochemical, and pathological analyses.

Results: Our research findings indicate that Atg5-deficient MSCs display heightened proliferative activity. Subsequent co-culturing of MSCs with hepatocytes and the transplantation of Atg5-deficient MSCs into NAFLD mouse models demonstrated their ability to effectively reduce lipid accumulation in the NAFLD disease model by modulating the AMPKα/mTOR/S6K/Srebp1 pathway. Furthermore, we observed that Atg5 deficiency enhances the secretion of hepatocyte growth factor (HGF) by promoting recycling endosome (RE) production. Lastly, our study revealed that 3-MA-primed MSCs can improve the characteristics of NAFLD by boosting the secretion of HGF.

Conclusions: Our research findings suggest that Atg5-deficient MSCs protect against NAFLD by accelerating HGF secretion. This indicates that Atg5 gene-modified MSCs may represent a promising strategy for treating NAFLD.

Substances (5)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Oleic acid 112-80-1 C18H34O2 1274 suppliers $4.00-$2495.75
Palmitic acid 57-10-3 C16H32O2 842 suppliers $5.00-$2109.25
3-METHYLADENINE 5142-23-4 C6H7N5 397 suppliers $12.00-$4500.00
CHLOROQUINE 54-05-7 C18H26ClN3 220 suppliers $5.00-$1550.00
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE 9001-50-7 C3H7O6P 181 suppliers $54.00-$921.00
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