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MiR-574-3p and miR-125a-5p in adipose derived mesenchymal stem cell exosomes synergistically target TGF-β1SMAD2 signaling pathway for the treatment of androgenic alopecia

ABSTRACT: Androgenetic alopecia (AGA) is the most common hair loss disorder, influenced by distinct genetic factors and intricate environmental factors. The exosomes (Exo) from adipose-derived mesenchymal stem cells (ADMSCs) have diverse effects, including the promotion of cell proliferation, inhibition of apoptosis, analgesia, and enhancement of wound healing. The miRNAs are essential components of the paracrine secretion of ADMSCs-Exo. This study revealed that ADMSCs-Exo could counteract the impairment of dermal papilla cells (DPCs) induced by dihydrotestosterone (DHT) by inhibiting the TGF-β1 signaling pathway`s activation.However, the exosomes derived from ADMSCs adipogenic differentiation (ADMSCsAd-Exo) lacked this therapeutic potential. Expression profiling of miRNAs in ADMSCs-Exo and ADMSCsAd-Exo by genomic microarray analysis. MiR-574-3p and miR-125a-5p, were identified as being predominantly expressed and specifically targeting TGF-β1 and SMAD2, respectively. Ultimately, our findings indicate that ADMSCs-Exo target the TGF-β1/SMAD2 signaling pathway via miR-574-3p and miR-125a-5p, are integral to their therapeutic action on DHT-induced DPCs and AGA murine models. This discovery offers significant insights into the pathogenesis of AGA and suggests potential therapeutic approaches. Further investigation into the role and interaction of these miRNAs in ADMSCs-Exo may lead to the development of more precise and efficacious treatments for AGA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281527 | GEO | 2025/04/17

REPOSITORIES: GEO

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Project description:Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy.

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MiR-574-3p and miR-125a-5p in adipose derived mesenchymal stem cell exosomes synergistically target TGF-β1SMAD2 signaling pathway for the treatment of androgenic alopecia

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