Journal of molecular histology · 2025
Mesenchymal stem cell exosomes regulate TGFβ/Smad3 by decreasing the METTL3-NEAT1 axis to inhibit scar progression after breast surgery.
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Du Juan, Wu Jincheng, Song Qinqin, Li Shuangru, Hong Youwang, Anwar Aizaz, Fu Quanyou, Liu Jisong
Аннотация
BACKGROUND: Scars are traces of tissue loss left behind by connective tissue overgrowth and repair. Studies in recent years have shown that mesenchymal stem cell exosomes (MSC-Exo) have the ability to inhibit and repair cutaneous scarring, but their specific role in post-breast surgery scar formation and the mechanisms behind it remain enigmatic.
METHODS: Extraction and characterization of exosomes from mesenchymal stem cells (MSCs). Western Blot and RT-qPCR were used to evaluate the expression of fibrillar protein and TGF-β/Smad3 in mammary hypertrophic scar fibroblasts (MHSFs) stimulated with MSC-Exo, sh-METTL3, sh-NEAT1 and their negative controls. Construction of a mouse model of proliferative scar formation using mechanical tension and detection of fibronectin and pathway protein expression using Western Blot and RT-qPCR. Pathologic changes of mammary scarring in mice using HE staining, Masson staining and immunofluorescence.
RESULTS: Both in vitro and in vivo, MSC-Exo, sh-METTL3 and sh-NEAT1 were shown to decrease the expression of COL1A1, COL3A1, α-SMA, fibronectin, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, by Western Blot and RT-qPCR. In addition, improved lesions and reduced collagen deposition were observed in mice by HE and Masson assays.
CONCLUSIONS: In summary, our study revealed that exosomes of MSCs function through the m6A methyltransferase METTL3, which regulates the NEAT1/TGF-β/Smad3 axis to slow down the rate of scar formation after breast surgery.
METHODS: Extraction and characterization of exosomes from mesenchymal stem cells (MSCs). Western Blot and RT-qPCR were used to evaluate the expression of fibrillar protein and TGF-β/Smad3 in mammary hypertrophic scar fibroblasts (MHSFs) stimulated with MSC-Exo, sh-METTL3, sh-NEAT1 and their negative controls. Construction of a mouse model of proliferative scar formation using mechanical tension and detection of fibronectin and pathway protein expression using Western Blot and RT-qPCR. Pathologic changes of mammary scarring in mice using HE staining, Masson staining and immunofluorescence.
RESULTS: Both in vitro and in vivo, MSC-Exo, sh-METTL3 and sh-NEAT1 were shown to decrease the expression of COL1A1, COL3A1, α-SMA, fibronectin, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, by Western Blot and RT-qPCR. In addition, improved lesions and reduced collagen deposition were observed in mice by HE and Masson assays.
CONCLUSIONS: In summary, our study revealed that exosomes of MSCs function through the m6A methyltransferase METTL3, which regulates the NEAT1/TGF-β/Smad3 axis to slow down the rate of scar formation after breast surgery.