PEITC promotes neurite growth in primary sensory neurons via the miR-17-5p/STAT3/GAP-43 axis

PEITC 通过 miR-17-5p/STAT3/GAP-43 轴促进初级感觉神经元的神经突生长

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作者:Zhijie Wang, Wenqi Yuan, Bo Li, Xueming Chen, Yanjun Zhang, Chuanjie Chen, Mei Yu, Yucai Xiu, Wenhua Li, Jiangang Cao, Xin Wang, Wen Tao, Xiaoling Guo, Shiqing Feng, Tianyi Wang

Abstract

The present study explored a key miRNA that plays a vital role in sciatic nerve conditioning injury promoting repair of injured dorsal column, and validated its function. Microarray analysis revealed miR-17-5p expression decreased sharply at 3, 7 and 14 days in the sciatic nerve conditioning injury group compared with the simple dorsal column lesion group. After miR-17-5p inhibition in DRG neurons, GAP-43 expression was upregulated and neurite growth was increased. STAT3 together with p-STAT3 showed opposite trends with miR-17-5p. MiR-17-5p inhibition extended neurite and upregulated STAT3, p-STAT3 and GAP-43. To further determine a substitution therapy for sciatic nerve conditioning injury, beta-phenethyl isothiocyanate (PEITC), which downregulates miR-17-5p, was assessed. The results showed that treatment with 10 µM PEITC resulted in longest neurite length. Further experiments demonstrated PEITC induced neurite growth by inhibiting miR-17-5p and further upregulating STAT3, p-STAT3 and GAP-43. The somatosensory evoked potential test confirmed similar treatment effects for PEITC, Ad-miRNA-17-5p inhibitor, and sciatic nerve conditioning injury on the dorsal column lesion. In conclusion, the miR-17-5p/STAT3/GAP-43 axis is an indispensable component of sciatic nerve conditioning injury promoting repair of injured dorsal column. PEITC could promote repair of injured dorsal column via the miR-17-5p/STAT3/GAP-43 axis, and could mimic the treatment effect of sciatic nerve conditioning injury.

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