(A) Slc38a5 mRNA levels were increased in human retinal microvascular endothelial cells (HRMECs) treated with Wnt ligands, recombinant Norrin, and Wnt3a-conditioned medium (Wnt3a-CM), compared with their respective vehicle controls (Ctrl, and Ctrl-CM), and suppressed by a Wnt inhibitor XAV939. (B–C) Protein levels of SLC38A5 in HRMECs were up-regulated by Wnt ligands Norrin (B) and Wnt3a-CM (C), and down-regulated by XAV939. Protein levels of SLC38A5 (52 kDa) and β-catenin (92 kDa) were quantified by Western blotting and normalized by glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 37 kDa) levels. n-p-β-catenin: non-phosphorylated β-catenin (92 kDa). (D) Three promoter regions upstream of Slc38a5 gene containing potential Wnt-responsive TCF (T-cell factor)-binding motifs (TTCAAAG) was identified based on sequence analysis. Three putative TCF-binding regions: P1 (–887 bp to –346 bp), P2 (–3925 bp to –3058 bp), and P3 (–5328 bp to –4423 bp) were cloned and ligated separately with a luciferase reporter, and co-transfected with an active β-catenin plasmid in HEK 293T cells, followed by measurement of luciferase activity. Data are expressed as mean ± SEM. (A-C) n=3–6 per group. (D) n=5 per construct group. *p≤0.05, **p≤0.01.
Figure 2—source data 1. Raw data for Figure 2.