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<p>Acute lung injury (ALI) is a life-threatening critical condition with high mortality. Adipose mesenchymal stem cell (ADMSC)-derived exosomes hold great potential for clinical therapy and drug delivery. Given that glutathione S-transferase Pi 1 (GSTP1), a key enzyme in oxidative stress response, is highly expressed in lung tissue and has been implicated in mitigating inflammatory and oxidative damage. However, the research on GSTP1-mediated ADMSC-derived exosomes in ALI is still blank.&#xa0;ADMSCs were characterized using flow cytometry, oil red O, Alizarin Red S, and clone formation assays. Gene expression was detected by quantitative real-time PCR (qRT-PCR) and western blotting. Exosomes were isolated and characterized by nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM), and their uptake was measured adopting the 3,3’-dioctadecyloxacarbocyanine perchlorate (DIO) probe. In vitro and in vivo ALI models were established exploiting lipopolysaccharide (LPS). Moreover, the cell viability, cytotoxicity, inflammatory response, cell apoptosis, oxidative stress markers, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) and adenosine 5’-triphosphate (ATP) levels, as well as hematoxylin-eosin (H&amp;E) staining were analyzed to evaluate the effects of GSTP1-modified exosomes on ALI.&#xa0;ADMSCs were positive for CD90 and CD73 and negative for CD34 and CD45. Exosomes were successfully isolated from ADMSCs, and GSTP1-modified exosomes exhibited enhanced uptake by human type II alveolar epithelial cells (HPAEpiCs). Furthermore, GSTP1-modified ADMSC exosomes attenuated LPS-induced inflammatory response, oxidative stress, mitochondrial dysfunction, and apoptosis in HPAEpiCs.&#xa0;GSTP1-modified exosomes derived from ADMSCs ameliorate ALI, suggesting a novel therapeutic target for this condition.</p> Graphical abstract <p>GSTP1 up-regulated ADMSC-derived exosomes inhibit inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction in LPS-induced ALI of HPAEpiCs.</p> <p></p>

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GSTP1-modified exosomes derived from ADMSCs relieve LPS-induced acute lung injury

  • 期刊论文

  • 发表日期：

    2025年12月5日

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  • Hong Guan,
  • Junkai Du,
  • Xiaoyan Wang,
  • Zhen Zhang,
  • Wanbo Zhou,
  • Feng Wang

摘要

Acute lung injury (ALI) is a life-threatening critical condition with high mortality. Adipose mesenchymal stem cell (ADMSC)-derived exosomes hold great potential for clinical therapy and drug delivery. Given that glutathione S-transferase Pi 1 (GSTP1), a key enzyme in oxidative stress response, is highly expressed in lung tissue and has been implicated in mitigating inflammatory and oxidative damage. However, the research on GSTP1-mediated ADMSC-derived exosomes in ALI is still blank. ADMSCs were characterized using flow cytometry, oil red O, Alizarin Red S, and clone formation assays. Gene expression was detected by quantitative real-time PCR (qRT-PCR) and western blotting. Exosomes were isolated and characterized by nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM), and their uptake was measured adopting the 3,3’-dioctadecyloxacarbocyanine perchlorate (DIO) probe. In vitro and in vivo ALI models were established exploiting lipopolysaccharide (LPS). Moreover, the cell viability, cytotoxicity, inflammatory response, cell apoptosis, oxidative stress markers, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) and adenosine 5’-triphosphate (ATP) levels, as well as hematoxylin-eosin (H&E) staining were analyzed to evaluate the effects of GSTP1-modified exosomes on ALI. ADMSCs were positive for CD90 and CD73 and negative for CD34 and CD45. Exosomes were successfully isolated from ADMSCs, and GSTP1-modified exosomes exhibited enhanced uptake by human type II alveolar epithelial cells (HPAEpiCs). Furthermore, GSTP1-modified ADMSC exosomes attenuated LPS-induced inflammatory response, oxidative stress, mitochondrial dysfunction, and apoptosis in HPAEpiCs. GSTP1-modified exosomes derived from ADMSCs ameliorate ALI, suggesting a novel therapeutic target for this condition.

Graphical abstract

GSTP1 up-regulated ADMSC-derived exosomes inhibit inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction in LPS-induced ALI of HPAEpiCs.