Phoenixin-14 Promotes the Recovery of Neurological Dysfunction After Spinal Cord Injury by Regulating Microglial Polarization via PTEN/Akt Signaling Pathway.
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引用次数: 3
Abstract
Spinal cord injury (SCI) is a destructive event in central nervous system (CNS) with the hallmark of deficits in neuronal function. Phoenixin-14 (PNX-14) is a reproductive peptide that also has neuroprotective effects. However, the role of PNX-14 in SCI has not yet been studied. In this study, we firstly investigated the effects of PNX-14 on the recovery of neurological dysfunction and microglial polarization in a SCI mice model. We demonstrated that PNX-14 improved the recovery of neurological dysfunction with increased Basso Mouse Scale (BMS) scores, reduced lesion area volume and Evans blue (EB) dye extravasation. PNX-14 alleviated neuronal apoptosis and neuroinflammation in mice underwent SCI. In vitro co-culture assay proved that PNX-14 protected neurons injury in response to LPS- activated BV-2 cells. PNX-14 suppressed the LPS- induced microglia M1 phenotype polarization with decreased expression of M1-associated markers (CD16 and iNOS) and increased expression of M2-associated markers (CD206 and Arg1). PNX-14 also suppressed LPS- caused decrease in anti-inflammatory cytokines TGF-β, IL-10, and IL-13, as well increase in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in BV2 cells. PNX-14 treatment caused increased PTEN expression and decreased p-Akt expression in BV2 cells against LPS induction. While inhibition of PTEN by SF1670 reversed the effects of PNX-14 on LPS- induced phenotypic transition of BV2 cells. Taken together, we found that PNX-14 exerted protective effects on neurological dysfunction and inflammation in SCI mice through modulating microglial polarization via PTEN/Akt signaling pathway.
期刊介绍:
Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods