Fig. 3

Molecular regulators and signalling mechanisms involved in the activation of astrocytes. The transformation of astrocytes from normal to reactive phenotypes involves a variety of intercellular and intracellular signalling mechanisms that trigger and maintain astrocytes reactivity.① Gp130-JAK-STAT3 signalling pathway. ② Notch-OLIG2 signalling pathway. ③ TGFβ-RGMa-SMAD signalling pathway. ④ Rac-GSPT1 signalling pathway. These signalling pathways regulate the expression of some genes that characterise reactive astrocytes, such as the genes that encode GFAP, CX43, and AQP4, and thus contribute to reactive astrogliosis. Furthermore, multiple signalling molecules in these signalling pathways promote the maintenance and development of chronic pain. IL, interleukin; LIF, leukaemia inhibitory factor; CNTF, ciliary neurotrophic factor; TGF-β, transforming growth factor-β; TNF-α, tumour necrosis factor-α; ET-1, endothelin-1; STAT3, signal transducer and activator of transcription 3; OLIG2, oligodendrocyte transcription factor 2; SMAD, Sma- and Mad-related protein; ROCK, rho associated kinase; GFAP, glial fibrillary acidic protein; CX43, connexin43; RII, type II receptor; ALK5, activatin-like kinase 5; JAK, janus kinase. GSPT1, G1 to S phase transition 1; RGMa, repulsive guidance molecule a