Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury.
Ciro De LucaAssunta VirtuosoMichele CerasuoloFrancesca GarganoAnna Maria ColangeloMarialuisa LavitranoGiovanni CirilloMichele PapaPublished in: Histochemistry and cell biology (2022)
Activation of glial cells (reactive gliosis) and the purinergic pathway, together with metalloproteinase (MMP)-induced remodeling of the neural extracellular matrix (nECM), drive maladaptive changes in the spinal cord following peripheral nerve injury (PNI). We evaluated the effects on spinal maladaptive plasticity through administration of oxidized ATP (oxATP), an antagonist of P2X receptors (P2XR), and/or GM6001, an inhibitor of MMPs, in rats following spared nerve injury (SNI) of the sciatic nerve. With morpho-molecular techniques, we demonstrated a reduction in spinal reactive gliosis and changes in the neuro-glial-nECM crosstalk via expression remodeling of P2XR, nerve growth factor (NGF) receptors (TrkA and p75), and histone deacetylase 2 (HDAC2) after treatments with oxATP/GM6001. Altogether, our data suggest that MMPs and purinergic inhibition have a modulatory impact on key proteins in the neuro-glial-nECM network, acting at different levels from intracellular signaling to epigenetic modifications.
Keyphrases
- peripheral nerve
- spinal cord
- neuropathic pain
- growth factor
- histone deacetylase
- extracellular matrix
- spinal cord injury
- poor prognosis
- induced apoptosis
- dna methylation
- gene expression
- cell cycle arrest
- cell death
- machine learning
- endothelial cells
- network analysis
- low density lipoprotein
- big data
- cell migration
- deep learning