microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling

Abstract

Astrogliosis following spinal cord injury (SCI) was considered as a negative factor for neural regeneration. We found that miR-21 was significantly upregulated after SCI. So, we aim to determine whether miR-21 acts in a positive manner post SCI. In vitro, we measured the proliferation, apoptosis and cytokine secretion of primary cultured astrocytes after modulating the expression of miR-21 by western blot, RT-PCR and immunofluorescence. In vivo, we performed a modified Allen’s weight drop model. Manipulation of the miR-21 expression level was achieved by interfering with antagomir and agomir. Clinic score was evaluated and recorded every day. Then, western blot, immunohistochemistry, TUNEL assay and ELISA were performed to detect pathological and functional alterations. Our results demonstrate that miR-21 can modulate the secretion, proliferation and apoptosis of astrocytes to promote recovery after SCI both in vivo and in vitro. These effects are likely mediated through transforming growth factor beta mediated targeting of the PI3K/Akt/mTOR pathway. These data suggest that miR-21 can regulate astrocytic function, then promote the functional recovery after SCI. We therefore highlight the positive effects of miR-21 after SCI.