Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy

Abstract

Aims. To investigate the candidate biomarkers and molecular mechanisms involved in the early phase of experimental diabetic peripheral neuropathy (DPN). Methods. Diabetes in Sprague-Dawley rats was induced with streptozotocin (STZ) treatment, followed with neurological tests and histological examinations to assess the neuropathic symptoms of DPN. Microarray was performed on the sciatic nerve tissues from control rats and DPN rats at then6th week after diabetes induction, and differentially expressed genes (DEGs) between them were identified and applied for further bioinformatic analyses. Results. Experimental DPN rats were successfully constructed, presenting significantly decreased withdrawal threshold and motor nerve conduction velocity, and typical histological changes in the sciatic nerve. 597 DEGs (186 up- and 411 downregulated) were identified in DPN rats. DEGs from the 3 most highly connected clusters in the protein-protein interaction network were enriched for biological processes or pathways such as “cell division,” “cell cycle,” “protein phosphorylation,” “chemokine signaling pathway,” “neuropeptide signaling pathway,” “response to drug,” “cellular response to insulin stimulus,” “PPAR signaling pathway,” and “glycerophospholipid metabolism.” Thirteen genes were identified as the hub DEGs in the PPI network. Eleven transcriptional factors (TFs) targeting 9 of the 13 hub DEGs were predicted. Conclusions. The present study identified a pool of candidate biomarkers such as Cdk1, C3, Mapk12, Agt, Adipoq, Cxcl2, and Mmp9 and molecular mechanisms which may be involved in the early phase of experimental DPN. The findings provide clues for exploring new strategies for the early diagnosis and treatment of DPN.

KLF11 enhances the effect of liraglutide in high glucoseinduced Schwann cells by regulating endoplasmic reticulum stress and autophagy through inactivation of P38 MAPK

“…Schwann is sensitive to insulin and glucose concentrations, and Schwann cell dysfunction is implicated in the development of DPN [4]. A previous study showed that KLF11, a diabetesrelated transcription factor, was downregulated in rats with diabetic peripheral neuropathy [8]. The effect of KLF11 on Schwann cells was investigated, and it was discovered that high glucose treatment reduced Schwann cell viability and promoted cell apoptosis [9], and high glucose-treated Schwann has been used as model of DPN [9].…”

“…KLF11 repressed gluconeogenesis and reduced cellular glucose output, thereby improving hyperglycemia and glucose intolerance in diabetic mice [7]. Moreover, KLF11 expression was downregulated in sciatic nerve tissues of streptozotocin-stimulated diabetic peripheral neuropathy rats [8]. Therefore, it has been hypothesized that KLF11 is involved in the pathogenesis of DPN.…”

Effect of Nano-eugenol and Aerobic Exercise Against the Streptozotocin Toxicity and Inflammatory Mediators P38-MAPK, NPY, and A-Rα2A in the Dorsal Root Ganglia of Diabetic Rats

“…The decline in NPY level was also evident in the spinal nerve roots of the rats in the treated area of DRG, which was associated with some degrees of spinal cord dystrophy. An earlier study has demonstrated increased volume and number of sprouting nerves subsequent to moderate intensity exercise in experimental rats [22]. Also, other studies have demonstrated that exercise has led to the adaptation, increased motor units and innervation of the muscles involved in exercising [23].…”

“…Although there is no experimental data available on the effect of nano-eugenol combined with concurrent exercise in experimental animals, our preliminary findings suggest that nano-eugenol provided and enhanced the level of antioxidant support such that neuronal damages due to diabetes could be reduced, repaired or prevented in experimental animals. In this context, further research is warranted to establish the cellular and molecular mechanisms by which the combination of aerobic exercise and nano-eugenol supplementation inhibit the destructive effects of diabetes in animal and human models [22,23].…”

The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus

“…A study reported that elevated spinal cord area index (SCAI) through upregulation can reduce the development of DPN by inhibiting the Wnt/β-catenin pathway upregulation [53]. This study suggested that targeting the SCAI signaling may be an alternative approach for treating DPN [53].…”