IMT504 enhances Wnt signaling pathway in GLAST+ Wnt1+ bone marrow stromal progenitors

BORDA M; CANTERO MJ; FIORE EF; GIARDELLI G; ALVARADO F; ABALO A; BECERRA C; MONTANER A; MAZZOLINI G; AQUINO JB

Mar del Plata

Congreso; Annual Meeting SAIC, SAB, AAF, AACYTAL; 2023

SAIC, SAB, AAF, AACYTAL

We previously found that the oligodeoxynucleotide IMT504 induces the proliferation and mobilization of GLAST+ Wnt1+ bone marrow stromal progenitors (BMPs), with no or little effects on other BMP subpopulations. Objectives: To evaluate the effect of IMT504 on the mRNA expression levels of ligands and markers of the Wnt signaling pathway in two subpopulations of BMSPs propagated in vitro. Materials and methods: Passaged 8 GLAST+ Tom+ and Tom- BMSP subfractions, obtained from GLASTCreERT2;Rosa26tdTomato (tamoxifen-injected at postnatal day 2), were incubated separately with the oligodeoxynucleotide (ODN) IMT504 for 2 hours and left to recover for 4 or 22 hours. The mRNA expression levels of Wnt ligands, as well as Wnt signaling pathway/target genes, were analyzed by qPCR. Results: A highly significant increase in Wnt1, Wnt3a and Wnt5a as well as in beta-catenin and Axin2, Lef1 and Sp5 was observed in GLAST+ Wnt1+ BMPs, without affecting Tom- cells. Consistently, a downregulation in E-cadherin was also observed in Tom+ cells treated with IMT504. And longer incubation after IMT504 treatment of Tom+ cells resulted in further significant changes in the mRNA expression levels of the same genes. Longer incubation after IMT504 treatment in serum-deprived culture medium appears to induce this expression pattern, even in naïve Tom+ cells. Conclusions: GLAST+ Wnt1+ BMPs are a unique cellular subpopulation, specifically targeted by IMT504, inducing the expression profile of Wnt ligands and signaling molecules, likely acting in an autocrine/paracrine manner to improve their proliferative and mobilization capabilities.