title: Insulin-like growth factor-II (IGF-II) and IGF-II analogs with enhanced insulin receptor-a binding affinity promote neural stem cell expansion.
abstract: The objective of this study was to employ genetically engineered IGF-II analogs to establish which receptor(s) mediate the stemness promoting actions of IGF-II on mouse subventricular zone neural precursors. Neural precursors from the subventricular zone were propagated in vitro in culture medium supplemented with IGF-II analogs. Cell growth and identity were analyzed using sphere generation and further analyzed by flow cytometry. F19A, an analog of IGF-II that does not bind the IGF-2R, stimulated an increase in the proportion of neural stem cells (NSCs) while decreasing the proportion of the later stage progenitors at a lower concentration than IGF-II. V43M, which binds to the IGF-2R with high affinity but which has low binding affinity to the IGF-1R and to the A isoform of the insulin receptor (IR-A) failed to promote NSC growth. The positive effects of F19A on NSC growth were unaltered by the addition of a functional blocking antibody to the IGF-1R. Altogether, these data lead to the conclusion that IGF-II promotes stemness of NSCs via the IR-A and not through activation of either the IGF-1R or the IGF-2R.
authors.affiliation: From the Department of Neurology and Neuroscience, Rutgers Biomedical and Health Sciences, Newark, New Jersey 07103-1709 and.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Ziegler
authors.forename: Shravanthi
authors.initials: S
authors.lastname: Chidambaram
authors.forename: Briony E
authors.initials: BE
authors.lastname: Forbes
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wood
authors.forename: Steven W
authors.initials: SW
authors.lastname: Levison
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D008024:Ligands; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin
keywords: Cell Proliferation; Central Nervous System; Insulin; Insulin Receptor; Neurodevelopment; Receptor Tyrosine Kinase; Self-renewal; Stem Cells