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. 2009 Jan 22;4(1):e4254. doi: 10.1371/journal.pone.0004254

Figure 3. IGFBP3 inhibits HCRT production in vivo and in vitro.

Figure 3

(A, B) Hypocretin-1 peptide content is significantly decreased in both hypothalamus and brainstem of IGFBP3 overexpressing transgenic mice (hIGFBP3 TG). In mutant IGFBP3 overexpressing mice (hmutIGFBP3 TG), the hypocretin-1 peptide shows slight but significant decrease only in brainstem, not in hypothalamus (A, B). Hypocretin mRNA is also significantly decreased in IGFBP3 (hIGFBP3 TG) mice but not in hmutIGFBP3 TG mice. (C) MCH mRNA level is not affected in hIGFBP3 TG or hmutIGFBP3 TG TG mice.(D) IGFBP3 expression reduces preprohypocretin promotor activity in the SH-SY5Y neuroblastoma cell line, but not in non-neural cell lines (HeLa, HEK, SF126, Becker). (F). In human subjects, rs2854744, −202 C, a promotor polymorphism allele known to be associated with reduced IGFBP3 production, is dose dependently associated with increased CSF hypocretin-1 levels. A, B: *: p<0.05; **, p<0.01; ***:p<0.001; C: *: p<0.001 versus without 3.2 kb promotor activity, #:p<0.001 versus promotor activity without IGFBP3; F: *: p<0.05 using ANOVA with genotype as a grouping factor. Sample numbers were indicated in parentheses.