{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:54:44Z","timestamp":1767833684391,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2015A030312016"],"award-info":[{"award-number":["2015A030312016"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870655"],"award-info":[{"award-number":["81870655"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Backgrounds<\/jats:title><jats:p>Insults to the axons in the optic nerve head are the primary cause of loss of retinal ganglion cells (RGCs) in traumatic, ischemic nerve injury or degenerative ocular diseases. The central nervous system\u2013specific leucine\u2010rich repeat protein, LINGO\u20101, negatively regulates axon regeneration and neuronal survival after injury. However, the upstream molecular mechanisms that regulate LINGO\u20101 signaling and contribute to LINGO\u20101\u2013mediated death of RGCs are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of SP1 was profiled in optic nerve crush (ONC)\u2013injured RGCs. LINGO\u20101 level was examined after SP1 overexpression by qRT\u2010PCR. Luciferase assay was used to examine the binding of SP1 to the promoter regions of LINGO\u20101. Primary RGCs from rat retina were isolated by immunopanning and RGCs apoptosis were determined by Tunnel. SP1 and LINGO\u20101 expression was investigated using immunohistochemistry and Western bolting. Neuroprotection was assessed by RGC counts, RNFL thickness, and VEP tests after inhibition of SP1 shRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that SP1 was upregulated in ONC\u2010injured RGCs. SP1 was bound to the LINGO\u20101 promoter, which led to increased expression of LINGO\u20101. Treatment with recombinant Nogo\u201066 or LINGO\u20101 promoted apoptosis of RGCs cultured under serum\u2010deprivation conditions, while silencing of SP1 promoted the survival of RGCs. SP1 and LINGO\u20101 colocalized and were upregulated in ONC\u2010injured retinas. Silencing of SP1 in vivo reduced LINGO\u20101 expression and protected the structure of RGCs from ONC\u2010induced injury, but there was no sign of recovery in VEP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings imply that SP1 regulates LINGO\u20101 expression in RGCs in the injured retina and provide insight into mechanisms underlying LINGO\u20101\u2013mediated RGC death in optic nerve injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13426","type":"journal-article","created":{"date-parts":[[2020,6,20]],"date-time":"2020-06-20T06:23:41Z","timestamp":1592634221000},"page":"1010-1020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SP1\u2010mediated upregulation of LINGO\u20101 promotes degeneration of retinal ganglion cells in optic nerve 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