MiR-17 targets PTEN and facilitates glial scar formation after spinal cord injuries via the PI3K/Akt/mTOR pathway.
We attempted to discover the regulatory role of miR-17 and PTEN in glial scar formation accompanied with spinal cord injuries.



We established a spinal cord injury (SCI) model in mice which were transfected with different groups of adenoviruses: miR-17 mimics, miR-17 inhibitors and PTEN cDNAs. The improvement of hind limb functions was assessed using the 21-point Basso-Beattie-Bresnahan (BBB) locomotion scale. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein (GFAP), Vimentin and neurofilaments. The expression of miR-17 was quantified using Real time-PCR (RT-PCR). Western blot was conducted to detect the expressions of PTEN, PI3K, Akt, mTOR and S6. Finally, dual luciferase reporter gene assay was conducted to confirm the target relationship between miR-17 and PTEN.



The model group exhibited significantly increased expression levels of GFAP, Vimentin, miR-17, PTEN, PI3K, Akt and mTOR. The above trend was enhanced by the transfection of miR-17 mimics (P<0.05). By contrast, the transfection of miR-17 inhibitors significantly down-regulated the expression of GFAP, Vimentin, PTEN, PI3K, Akt, mTOR and p-S6 whereas the expression of GFAP, Vimentin, PI3K, Akt, mTOR and p-S6 in the cells transfected with PTEN cDNAs significantly decreased (P<0.05). Also, the transfection of miR-17 inhibitors and PTEN cDNAs alleviated the astrogliosis in SCI lesions, contributed to the regeneration of nerve filament and improved the functional recovery of the hind limb of mice. Finally, the targeting relationship between miR-17 and PTEN was verified by the dual luciferase reporter gene assay.



MiR-17 is able to target PTEN and stimulate the PI3K/Akt/mTOR pathway. The formation of glial scar resulted from spinal cord injuries can be reduced either by inhibiting miR-17 or by overexpressing PTEN.
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021 Jilin, China.
Yongxin
Y
Luan
Jilin Province People's Hospital, Changchun, 130000 Jilin, China.
Mo
M
Chen
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021 Jilin, China. Electronic address: zhoulixiang16@163.com.
Lixiang
L
Zhou
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D014746:Vimentin; C543614:Mirn17 microRNA, mouse; C528900:glial fibrillary astrocytic protein, mouse; C546843:mTOR protein, mouse; C487757:Pten protein, mouse
Glial scar formation; MiR-17; PI3K/Akt/mTOR; PTEN; Spinal cord injury