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.

De Luca, C., Virtuoso, A., Cerasuolo, M., Gargano, F., Colangelo, A., Lavitrano, M., et al. (2022). Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury. HISTOCHEMISTRY AND CELL BIOLOGY, 157(5), 557-567 [10.1007/s00418-022-02082-4].

Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury

Colangelo A. M.;Lavitrano M.;
2022

Abstract

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.
Articolo in rivista - Articolo scientifico
Extracellular matrix; Peripheral nerve injury; Reactive gliosis; Spinal cord; Systems biology;
English
557
567
11
De Luca, C., Virtuoso, A., Cerasuolo, M., Gargano, F., Colangelo, A., Lavitrano, M., et al. (2022). Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury. HISTOCHEMISTRY AND CELL BIOLOGY, 157(5), 557-567 [10.1007/s00418-022-02082-4].
De Luca, C; Virtuoso, A; Cerasuolo, M; Gargano, F; Colangelo, A; Lavitrano, M; Cirillo, G; Papa, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/355819
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