Promotion of the Differentiation of Dental Pulp Stem Cells into Oligodendrocytes by Knockdown of Heat-Shock Protein 27

Stem cell-based therapy has been evaluated in many different clinical trials for various diseases. This capability was applied in various neurodegenerative diseases, such as Alzheimer’s disease, which is characterized by synaptic damage accompanied by neuronal loss. Dental pulp stem cells (DPSCs) are mesenchymal stem cells from the oral cavity and have been studied with potential application for regeneration of different tissues. Heat shock protein 27 (HSP27) is known to regulate neurogenesis in the process of neural differentiation of placenta-multipotent stem cells. Here, we hypothesize that HSP27 expression is also critical in neural differentiation of DPSCs. An evaluation of the possible role of HSP27 in differentiation of DPSCs was per-formed by gene knockdown and neural immunofluorescent staining. We found that HSP27 has a role in the differentiation of DPSCs and that knockdown of HSP27 in DPSCs renders cells to oligodendrocyte progenitors. In other words, shHSP27-DPSCs showed NG2-positive immunoreactivity and gave rise to oligodendrocytes or type-2 astrocytes. This neural differentiation of DPSCs may have clinical significance for treatment of patients with neurodegenerative diseases. In conclusion, our data provide an example of oligodendrocyte differentiation of a DPSCs model that may have potential application in human regenerative medicine.

Neflamapimod Induces Vasodilation in Resistance Mesenteric Arteries by Inhibiting p38 Mitogen-Activated Protein Kinase Alpha (MAPKα) and Heat-Shock Protein 27 (Hsp27) Phosphorylation

Neflamapimod, a selective inhibitor of p38 MAPKα, is under clinical investigation for its efficacy in Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB). Here, we investigated if neflamapimod-mediated acute inhibition of p38 MAPKα could induce vasodilation in resistance-size rat mesenteric arteries. Our pressure myography data demonstrated that neflamapimod produced a dose-dependent vasodilation in mesenteric arteries. Our Western blotting data revealed that acute neflamapimod treatment significantly reduced the phosphorylation of p38 MAPKα and its downstream target heat-shock protein 27 (Hsp27) that is involved in cytoskeletal reorganization and smooth muscle contraction. Likewise, non-selective inhibition of p38 MAPK by SB203580 attenuated p38 MAPKα and Hsp27 phosphorylation, and induced vasodilation. Endothelium denudation or pharmacological inhibition of endothelium-derived vasodilators such as nitric oxide (NO) and prostacyclin (PGI2) had no effect on such vasodilation. Neflamapimod-evoked vasorelaxation remained unaltered by the inhibition of smooth muscle cell K+ channels. Altogether, our data for the first time demonstrates that in resistance mesenteric arteries, neflamapimod inhibits p38 MAPKα and phosphorylation of its downstream actin-associated protein Hsp27, leading to vasodilation. This novel finding may be clinically significant and is likely to improve systemic blood pressure and cognitive deficits in AD and DLB patients for which neflamapimod is being investigated.

Effect of aerobic training on heat shock protein 27 and brain-derived neurotrophic factor in hippocampus and prefrontal cortex of type II diabetic rats

Background: According to the experimental studies, the levels of heat shock protein 27 (HSP27) and brain-derived neurotrophic factor (BDNF) are decreased in diabetes which is associated with impaired cognitive function in the brain. Therefore, the increased expression of these two proteins in some brain regions associated with learning and memory can be one of the positive effects of aerobic training on cognition improvement at diabetes. The aim of the present study was to evaluate the effects of aerobic treadmill exercise training (ATET) on HSP27 and BDNF proteins in the prefrontal cortex and hippocampus of streptozotocin (STZ)-induced diabetes in rats. Methods: Twenty healthy adult male Wistar rats approximately 3-month old, weighing 250 ± 25gr were used in this study. Experimental diabetes was induced by a high-fat diet (HFD) for 4 weeks and a low dose of STZ (35 mg/kg, intraperitoneally). Then diabetic animals were divided into two groups (n=10 per each group): control group (C) and aerobic training group (E). The exercise program was treadmill running at 13 m/min, 25 min/day, for 5 days/week at 0˚ slope for the first week, with a gradual increase to 27 m/min for 60 min/day in week 8. Un-paired t-test was used to compare two groups with the considered significant at p<0.05. Results: The results showed that ATET significantly increased protein expression of HSP27 and BDNF in the hippocampus and prefrontal cortex as compared to C group. Conclusion: Our findings showed that aerobic treadmill exercise program can increase the protein expression of HSP27 and BDNF associated with cognition and synaptic plas­ticity and thus counteract the neurodegenerative diseases of the nervous system.