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

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Spinal cord injury (SCI) makes a major contribution to disability and death in the 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 higher expression of interleukin (IL)-6, IL-1β and BDNF in LPS-stimulated NHAs. BDNF significantly promoted normal human astrocyte (NHA) proliferation. Further, online tools were employed to screen for the candidate miRNAs which might directly target BDNF to inhibit its expression. Among the candidate miRNAs, miR-211 expression was downregulated by LPS stimulation in a dose-dependent manner. Through direct targeting, miR-211 inhibited BDNF expression. Ectopic miR-211 expression significantly suppressed NHA proliferation, as well as LPS-induce activation of PI3K/Akt pathway. In contrast, inhibition of miR-211 expression significantly promoted NHA proliferation and LPS-induce 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.

This publication has 49 references indexed in Scilit: