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.

Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy

“…In vivo and in vitro inhibition of the TGF-β pathway blocks the function of fibrinogen in the glial scar formation [64]. It is worth mentioning that our team has found that miR-21 regulates reactive astrogliosis by TGF-β signaling at the postacute phase of SCI [65]. More recently, we demonstrated that miR-21 is a switch that regulates the polarization of astrocytes.…”

Silencing miR‐21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 via the signal transducer and activator of transcription‐3 pathway after acute ischemic spinal cord injury

“…Our previous studies suggested that miR-21 regulates astrocytic reactions after the acute phase of spinal cord injury by modulating TGF-b signaling; miR-21 was up-regulated and diminished the neuroprotection of neurons (17). Therefore, we tried to verify that silencing miR-21 would promote the neuroprotective development of astrocytes.…”

“…Accumulating evidence has implicated miR in the recovery from ischemic diseases: miR-17-3p promoted motor-induced chamber velocity, cardiac growth, and prevented disadvantageous ventricular remodeling (14). Moreover, miR-424 contributed to postischemic-induced vascular remodeling and angiogenesis (15); miR-92a may be an important therapeutic target for the treatment of heart ischemic disease in pigs (16); and miR-21 has been observed to participate in regulating astrocytic reaction to postacute spinal cord injury via the TGF-b pathway (17), thereby suggesting that miR-21 performs various vital functions in ISCI.…”

Astrocytes: News about Brain Health and Diseases

“…Analogous effects were obtained by inducing an astrocyte miRNA, miR-21. Upon the activation of TGF-β1, miR-21 is known to induce profound positive changes in astrocyte responses, mediated by an important signaling pathway [ 52 ]. In contrast, the activation of another miRNA, miR-335-3p, was found to increase the severity of negative astrocyte responses by changing the properties of their metabolic effects [ 53 ].…”

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury

“…However, the controversy about scientific evidence of neuroprotective and regenerative therapies for SCI has raged unabated for ages. Recently, extensive evidence related to the noncoding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs; Zhang et al, 2018a,b), microRNAs (miRNAs; Liu et al, 2018), and circular RNAs (circRNAs; Qin et al, 2019), maybe at the point of breaking this impasse. The existing research has identified the critical role of these ncRNAs in alleviating the secondary pathophysiological damage after SCI (Jiang and Zhang, 2018;Wang et al, 2019).…”