{"doi":"10.17615/9nep-bc45","title":"β-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial cultures","abstract":"By promoting cell proliferation, survival and maturation insulin-like growth factor (IGF)-I is essential to the normal growth and development of the central nervous system. It is clear that IGF-I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)-Akt kinases and MAP kinases signal many of IGF-I-IGF1R actions in neural cells, including oligodendrocyte lineage cells. The precise downstream targets of these signaling pathways, however, remain to be defined. We studied oligodendroglial cells to determine whether β-catenin, a molecule that is a downstream target of glycogen synthase kinase-3β (GSK3β) and plays a key role in the Wnt canonical signaling pathway, mediates IGF-I actions. We found that IGF-I increases β-catenin protein abundance within an hour after IGF-I-induced phosphorylation of Akt and GSK3β. Inhibiting the PI3-Akt pathway suppressed IGF-I-induced increases in β-catenin and cyclin D1 mRNA, while suppression of GSK3β activity simulated IGF-I actions. Knocking-down β-catenin mRNA by RNA interference suppressed IGF-I-stimulated increases in the abundance of cyclin D1 mRNA, cell proliferation, and cell survival. Our data suggest that β-catenin is an important downstream molecule in the PI3-Akt-GSK3β pathway, and as such it mediates IGF-I upregulation of cyclin D1 mRNA and promotion of cell proliferation and survival in oligodendroglial cells.","journal":"UNC Libraries","year":2020,"id":140473,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":121280,"name":"A. Joseph D'ercole","orcid":null,"position":1,"is_corresponding":false},{"id":524325,"name":"Hedi Liu","orcid":null,"position":2,"is_corresponding":false},{"id":523416,"name":"Ping Ye","orcid":"0000-0002-5591-6812","position":3,"is_corresponding":false},{"id":523415,"name":"Qichen Hu","orcid":"0009-0007-1924-1807","position":4,"is_corresponding":false},{"id":604707,"name":"Yun Yan","orcid":"0000-0001-8759-3918","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:17.077903Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}