MicroRNA-211/BDNF axis regulates LPS-induced proliferation of normal human astrocyte through PI3K/AKT pathway

Abstract

Spinal cord injury (SCI) makes a major contribution to disability and deaths worldwide. Reactive astrogliosis, a typical feature after SCI, which undergoes varying molecular and morphological changes, is ubiquitous but poorly understood. Reactive astrogliosis contributes to glial scar formation that impedes axonal regeneration. Brain-derived neurotrophic factor (BDNF), a well-established neurotrophic factor, exerts neuroprotective and growth-promoting effects on a variety of neuronal populations after injury. In the present study, by using LPS-induced in vitro injury model of astroglial cultures, we observed a high expression of interleukin (IL)-6, IL-1β, and BDNF in LPS-stimulated normal human astrocytes (NHAs). BDNF significantly promoted NHA proliferation. Further, online tools were employed to screen the candidate miRNAs which might directly target BDNF to inhibit its expression. Amongst the candidate miRNAs, miR-211 expression was down-regulated by LPS stimulation in a dose-dependent manner. Through direct targetting, miR-211 inhibited BDNF expression. Ectopic miR-211 expression significantly suppressed NHA proliferation, as well as LPS-induced activation of PI3K/Akt pathway. In contrast, inhibition of miR-211 expression significantly promoted NHA proliferation and LPS-induced activation of PI3K/Akt pathway. Taken together, miR-211/BDNF axis regulates LPS-induced NHA proliferation through PI3K/AKT pathway; miR-211/BDNF might serve as a promising target in the strategy against reactive astrocyte proliferation after SCI.

Ligustrazine Inhibits Growth, Migration and Invasion of Medulloblastoma Daoy Cells by Up-Regulation of miR-211

“…Recent study have stated that miR-211 could modulate inflammatory diseases through regulating PI3K/AKT pathway [28]. Further, LSZ has been proven to be an important regulator of the PI3K/AKT pathway [29,30].…”

Isoflurane Regulates Proliferation, Apoptosis, and Inflammatory Response of Lipopolysaccharide-Induced Human Astrocyte through the miR-206/BDNF Axis

“…NHAs. qPCR results showed that LPS significantly inhibited the expression of miRNAs [2,[11][12][13] associated with proliferation and apoptosis of NHAs (p < 0:05, p < 0:01), and the addition of ISO reversed these inhibitory effects to a certain extent. In particular, among all examined miRNAs, miR-206 was the most significantly reversed one (Figure 2, p < 0:01).…”

“…It has been reported that the normal human astrocytes (NHAs) can minimize primary damage and repair damaged tissues. However, under certain pathological conditions, NHAs can change to become reactive NHAs [2], and reactive NHAs are one of the main sources of proinflammatory cytokines in the brain [3]. NHAs are involved in the development of a variety of neurodegenerative diseases [4]; therefore, studying the mechanism of reactive NHAs is helpful for the development of protective strategies for neurodegenerative diseases induced by central nervous system inflammation.…”

Neuroinflammation in the central nervous system: Symphony of glial cells

“…Some microRNAs also affect the polarization of microglia to regulating inflammation. For example, miR-125b promotes toxic M1 polarization, and miR-124 contributes to protective M2 polarization of microglia (Parisi et al, 2016;Yu et al, 2017) -140, miR-211, miR-145, miR-146a, miR-147b, miR-132, and miR-181, not only inhibit the production of pro-inflammation factors but also act against reactive astrocyte proliferation through the PI3K/AKT pathway (Hutchison et al, 2013;Iyer et al, 2012;Tu et al, 2017;Van Scheppingen et al, 2018;Wang, Yang, & Tzeng, 2015;Zhang, Wu, Li, & Zhou, 2017; expression (Dentesano et al, 2014). The suppression of neuroinflammation can also be mediated by modulating the signaling of additional pairs of interacting molecules, such as CD22-CD45, CD172A-CD47, and ICAM5-leukocyte β2-integrins (Gahmberg, Tian, Ning, & Nyman-Huttunen, 2008;Mott et al, 2004;Numakawa et al, 2004).…”