Adipose Stem Cell Exosomes Promote Mitochondrial Autophagy Through the PI3K/AKT/mTOR Pathway to Alleviate Keloids

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2024 Sep 15

PMID 39278919

Authors

Chang Liu

Liliia Khairullina

Youyou Qin

Yingbo Zhang

Zhibo Xiao

Affiliations

Soon will be listed here.

Abstract

Background: Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids.

Method: We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20-22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo.

Results: ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments.

Conclusions: Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars.

Citing Articles

MSCs-derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K/AKT/mTOR axis.

Elsherbiny N, Abdel-Maksoud M, Prabahar K, Mohammedsaleh Z, Badr O, Dessouky A J Ovarian Res. 2024; 17(1):222.

PMID: 39529187 PMC: 11552115. DOI: 10.1186/s13048-024-01545-7.

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