19 Harley St, London, W1G 9QJ, UK

Genetic Targeting of Protease Activated Receptor 2 Reduces Inflammatory Astrogliosis and Improves Recovery of Function after Spinal Cord Injury.

Related Articles

Genetic Targeting of Protease Activated Receptor 2 Reduces Inflammatory Astrogliosis and Improves Recovery of Function after Spinal Cord Injury.

Neurobiol Dis. 2015 Aug 24;

Authors: Radulovic M, Yoon H, Wu J, Mustafa K, Fehlings MG, Scarisbrick IA

Inflammatory-astrogliosis exacerbates damage in the injured spinal cord and limits repair. Here we identify Protease Activated Receptor 2 (PAR2) as an essential regulator of these events with mice lacking the PAR2 gene showing greater improvements in motor coordination and strength after compression-spinal cord injury (SCI) compared to wild type littermates. Molecular profiling of the injury epicenter, and spinal segments above and below, demonstrated mice lacking PAR2 had significantly attenuated elevations in key hallmarks of astrogliosis (glial fibrillary acidic protein (GFAP), vimentin and neurocan) and in expression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF) and interleukin -1 beta (IL-1?)). SCI in PAR2-/- mice was also accompanied by improved preservation of protein kinase C gamma (PKC?)-immunopositive corticospinal axons and reductions in GFAP-immunoreactivity, expression of the pro-apoptotic marker BCL2-interacting mediator of cell death (BIM), and in signal transducer and activator of transcription 3 (STAT3). The potential mechanistic link between PAR2, STAT3 and astrogliosis was further investigated in primary astrocytes to reveal that the SCI-related serine protease, neurosin (kallikrein 6) promotes IL-6 secretion in a PAR2 and STAT3-dependent manner. Data point to a signaling circuit in primary astrocytes in which neurosin signaling at PAR2 promotes IL-6 secretion and canonical STAT3 signaling. IL-6 promotes expression of GFAP, vimentin, additional IL-6 and robust increases in both neurosin and PAR2, thereby driving the PAR2-signaling circuit forward. Given the significant reductions in astrogliosis and inflammation as well as superior neuromotor recovery observed in PAR2 knockout mice after SCI, we suggest this receptor and its agonists represent new drug targets to foster neuromotor recovery.

PMID: 26316358 [PubMed – as supplied by publisher]

Share to care...

Share on facebook
Share on twitter
Share on pinterest
Share on google
Share on linkedin
Share on skype

What we do...

The Harley Street Hospital


What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

We treat all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

What our patients say about us ......