Pu.1 mimic synthetic peptides selectively bind with gata-1 and allow c-jun pu.1 binding to enhance myelopoiesis

Abstract

Background: Hematopoietic stem cells' commitment to myelopoiesis builds immunity to prevent infection. This process is controlled through transcription factor, especially Purine rich box 1 (PU.1) protein, which plays a central role in regulating myelopoiesis. The β3/β4 region of PU.1 accommodates a coactivator transcription factor, c-Jun, to activate myelopoiesis. However, an erythroid transcription factor, GATA-1, competes with c-Jun for the β3/β4 region, abolishing myelopoiesis and promoting erythropoiesis. This competitive regulation decides the hematopoietic stem cells’ commitment towards either erythroid or myeloid lineage. Methods: Therefore, this study investigated the in vitro and in vivo effect of novel synthetic PU.1 β3/β4 mimic peptide analogs and peptide-loaded hydrophilic poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Results: The designed peptides significantly increase the expression of corresponding myeloid markers, specifically CD33 in vitro. However, the in vivo delivery of peptide-loaded PLGA nanoparticles, which have sustained release effect of peptides, increases 10.8% of granulocytes as compared to control. Conclusion: The observations showed that the fabricated nanoparticles protected the loaded peptides from the harsh intracellular environment for a longer duration without causing any toxicity. These findings highlight the possibility to use these peptides and peptide-loaded nanoparticles to increase hematopoietic stem cell commitment to myeloid cells in case of opportunistic infection.