title: LXR agonists promote the proliferation of neural progenitor cells through MEK-ERK pathway.
abstract: The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis and may be critical for neurodegeneration and neurogenesis in vivo. However, it remains largely unknown about the role of LXRs and its agonists in the in vitro proliferation of neural progenitor cells (NPCs). Here we revealed for the first time that LXRs were markedly expressed in mouse NPCs and were critical for the in vitro proliferation. LXR agonists GW3965 and LXR623 promoted the proliferation of wildtype NPCs, but not NPCs from LXR double-knockout mice. Mechanistically, phosphorylation of MEK1/2 and ERK1/2 in NPCs was enhanced upon LXR agonist treatment, while abrogation of MEK/ERK phosphorylation by the inhibitors PD98059 and U0126 impaired the proliferation of wildtype NPCs in the presence or absence of LXR agonists. Collectively, our findings suggest that LXR agonists GW3965 and LXR623 can stimulate the NPC proliferation in LXR- and MEK/ERK-dependent manner.
authors.affiliation: Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China. Electronic address: jingzhongwang1@sina.cn.
authors.forename: Jing-Zhong
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Ji
authors.affiliation: Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D007191:Indazoles / Q000494:pharmacology*; D000071518:Liver X Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: C547927:2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole; D001565:Benzoates; D001596:Benzylamines; D005419:Flavonoids; C473027:GW 3965; D007191:Indazoles; D000071518:Liver X Receptors; D047428:Protein Kinase Inhibitors; D020930:MAP Kinase Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: GW3965; GW3965 (Pubche CID: 447905); LXR agonists; LXR623; LXR623 (Pubche CID: 16734800); Neural progenitor cells; PD98059 (Pubche CID: 4713); Proliferation; SP600125 (Pubche CID: 8515); U0126 (Pubche CID: 3006531)