The bone marrow-derived mesenchymal stem cells (BMSCs) alleviate diabetic peripheral neuropathy induced by STZ via activating GSK-3β/β-catenin signaling pathway

Environ Toxicol Pharmacol. 2020 Oct:79:103432. doi: 10.1016/j.etap.2020.103432. Epub 2020 Jun 2.

Abstract

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.

Keywords: BMSCs; Diabetic peripheral neuropathy; GSK-3β/β-catenin signaling pathway.

MeSH terms

  • Animals
  • Blood Glucose
  • Body Weight
  • Bone Marrow Cells / cytology
  • Cell Survival
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / therapy*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Oxidative Stress
  • Rats, Sprague-Dawley
  • Schwann Cells
  • beta Catenin / metabolism

Substances

  • Blood Glucose
  • Ctnnb1 protein, rat
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat