Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway
Yu Xia1 · Lu Ding1 · Changlin Zhang2,3 · Qi Xu1 · Ming Shi1 · Tianshun Gao4 · Feng‑Quan Zhou5 · David Y. B. Deng1,61 Scientifc Research Center, The Seventh Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
2 Department of Gynecology, The Seventh Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
3 Pelvic Floor Disorders Center, The Seventh Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
4 Big Data Center, The Seventh Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
5 Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
6 Orthopaedic and Neurological Repair Center, The Seventh Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Abstract
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 Ca2+ transport functions were inhibited in astrocytes after SCI. Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca2+/calmodulin-dependent protein kinase 2b (CaMK2b) pathway in vitro. By screening different inflammatory factors, interleukin 1α (IL1α) was further found to inhibit Grin2c/Ca2+/CaMK2b and enhance astrocyte proliferation in an oxidative damage model. Blockade of IL1α using neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI. Overall, this study suggests that IL1α promotes astrocyte proliferation by suppressing the Grin2c/Ca2+/CaMK2b pathway after SCI, revealing a novel pathological mechanism of astrocyte proliferation, and may provide potential targets for SCI repair.
Keywords
IL1α; Grin2c; Astrocyte; Spinal cord injury
