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The bone marrow-derived mesenchymal stem cells (BMSCs) alleviate diabetic peripheral neuropathy induced by STZ via activating GSK-3β/β-catenin signaling pathway.
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2020-06-02 , DOI: 10.1016/j.etap.2020.103432
Dingwen He 1 , Yanjie Xu 2 , Xi Xiong 3 , Changchang Yin 4 , Shuihong Lei 5 , Xigao Cheng 1
Affiliation  

Background

Diabetic peripheral neuropathy, a common complication of diabetic mellitus, has brought a threaten on patients’ health. The bone marrow-derived mesenchymal stem cells (BMSCs) were reported to play an important role in diverse diseases. Nevertheless, the specific function of BMSCs in diabetic peripheral neuropathy remained uncharacterized.

Methods

A wide range of experiments including RT-qPCR, western blot, H&E staining, oxidative stress assessment, measurement of thermal sensitivity, ELISA, urine protein and CCK-8 assays were implemented to explore the function and mechanism of BMSCs in vivo and vitro.

Results

The experimental results displayed that BMSCs improve STZ-induced diabetes symptoms in rats by decreasing blood glucose and urinary protein. Functionally, BMSCs ameliorate oxidative stress, painful diabetic neuropathy, neurotrophic status and angiogenesis in STZ-induced rats. Moreover, BMSCs participate in the regulation of sciatic neuro morphology in diabetic neuropathy rat model. In mechanism, BMSCs alleviate diabetic peripheral neuropathy via activating GSK-3β/β-catenin signaling pathway in rats and improve Schwann's cells viability by activating GSK-3β/β-catenin signaling pathway under high glucose.

Conclusions

We verified that BMSCs alleviate diabetic peripheral neuropathy of rats induced by STZ via activating GSK-3β/β-catenin signaling pathway, which implied a novel biomarker for diabetic peripheral neuropathy treatment.



中文翻译:

骨髓来源的间充质干细胞(BMSC)通过激活GSK-3β/β-catenin信号通路减轻STZ诱导的糖尿病周围神经病变。

背景

糖尿病周围神经病变是糖尿病的常见并发症,已经威胁到患者的健康。据报道,骨髓间充质干细胞(BMSC)在多种疾病中起重要作用。然而,BMSCs在糖尿病周围神经病变中的特定功能仍未表征。

方法

进行了广泛的实验,包括RT-qPCR,蛋白质印迹,H&E染色,氧化应激评估,热敏性测量,ELISA,尿蛋白和CCK-8分析,以探索BMSCs在体内和体外的功能和机制。

结果

实验结果表明,骨髓间充质干细胞通过降低血糖和尿蛋白来改善STZ诱导的糖尿病糖尿病症状。在功能上,BMSC改善了STZ诱导的大鼠的氧化应激,糖尿病性神经病变,神经营养状态和血管生成。此外,BMSCs参与糖尿病性神经病大鼠模型中坐骨神经形态的调节。在机制上,骨髓间充质干细胞通过激活大鼠中的GSK-3β/β-catenin信号通路来减轻糖尿病周围神经病变,并通过在高葡萄糖下激活GSK-3β/β-catenin信号通路来改善雪旺氏细胞的生存能力。

结论

我们证实,骨髓间充质干细胞通过激活GSK-3β/β-catenin信号通路减轻了STZ所致大鼠的糖尿病周围神经病变,这暗示了糖尿病周围神经病变治疗的新型生物标志物。

更新日期:2020-06-02
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