Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI i...Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.展开更多
基金supported by the National Natural Science Foundation of China(82071362,82002899)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ202205303001577,JCYJ20190809165201646)Basic Research Projects of Shenzhen Science and Technology Program(JCYJ20180307150610733).
文摘Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.
