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Delivery of miR-130a-3p Through Adipose-Derived Stem Cell-Secreted EVs Protects Against Diabetic Peripheral
Ji Chen1, Gengzhang Li2, Xinxin Liu3
1Department of Endocrinology, The First People's Hospital of Huaihua, Huaihua, 418000, People's Republic of China.
Abstract:
Peripheral neuropathy is common in diabetic patients and can lead to amputations or foot ulcers. microRNAs (miRNAs) possess crucial roles in diabetic peripheral neuropathy (DPN). This study aims to investigate the role miR-130a-3p played in DPN and its underlying molecular mechanisms. miR-130a-3p expression in clinical tissue samples, established DPN rat models, and extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSCs) were determined. Schwann cells (SCs) were co-cultured with ADSC-derived EVs and treated with high glucose. The direct relationship and functional significance of miR-130a-3p, DNMT1, nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor-1α (HIF1α), and skeletal muscle actin alpha 1 (ACTA1) was identified. The in vitro and in vivo implication of ADSC-derived EVs carrying miR-130a-3p was assessed. miR-130a-3p was poorly expressed in DPN patients and rats but highly expressed in ADSC-derived EVs. miR-130a-3p could be delivered to SCs through ADSC-derived EVs to inhibit SC apoptosis and promote proliferation under a high-glucose environment. miR-130a-3p activated NRF2/HIF1α/ACTA1 axis through down-regulating DNMT1. In vivo injection of ADSC-derived EVs activated NRF2/HIF1α/ACTA11 axis to promote angiogenesis in DPN rat model. These data together supported that ADSC-derived EVs carrying miR-130a-3p could alleviate DPN by accelerating SC proliferation and inhibiting apoptosis, providing a potential treatment against DPN.
Insights
Adipose-derived stem cell extracellular vesicles carrying miR-130a-3p can treat diabetic peripheral neuropathy (DPN) by promoting Schwann cell proliferation and inhibiting apoptosis. This novel therapy targets the NRF2/HIF1α/ACTA1 pathway, offering a potential DPN treatment.
Area of Science:
- Biomedical research
- Molecular biology
- Stem cell therapy
Background:
- Diabetic peripheral neuropathy (DPN) is a common complication leading to severe outcomes.
- MicroRNAs (miRNAs) are implicated in the pathogenesis of DPN.
- Identifying novel therapeutic targets for DPN is crucial.
Purpose of the Study:
- To investigate the role of miR-130a-3p in DPN.
- To elucidate the molecular mechanisms underlying miR-130a-3p's function in DPN.
- To assess the therapeutic potential of adipose-derived stem cell (ADSC)-derived extracellular vesicles (EVs) carrying miR-130a-3p for DPN.
Main Methods:
- Determined miR-130a-3p expression in clinical samples, DPN rat models, and ADSC-derived EVs.
- Co-cultured Schwann cells (SCs) with ADSC-derived EVs under high glucose conditions.
- Investigated the regulatory axis involving miR-130a-3p, DNMT1, NRF2, HIF1α, and ACTA1 in vitro and in vivo.
Main Results:
- miR-130a-3p expression was reduced in DPN patients and rats but abundant in ADSC-derived EVs.
- ADSC-derived EVs delivered miR-130a-3p to SCs, inhibiting apoptosis and promoting proliferation in high glucose.
- miR-130a-3p activated the NRF2/HIF1α/ACTA1 pathway by downregulating DNMT1, promoting angiogenesis in DPN rats.
Conclusions:
- ADSC-derived EVs carrying miR-130a-3p can alleviate DPN.
- This therapeutic strategy enhances SC proliferation and inhibits apoptosis via the NRF2/HIF1α/ACTA1 axis.
- This approach presents a promising therapeutic avenue for DPN treatment.
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