Silica Nanoparticles Promote the Megakaryocyte Maturation and Differentiation: Potential Implications for Hematological Homeostasis

Silica nanoparticles (SiO2 NPs) have beenwidely appliedin diverse areas, thus causing the extensive release through multipleroutes. Their toxicological effects, especially for the disturbancein hematological homeostasis, have raised public concern. Consideringthe detrimental role of excessive platelets in many cardiovasculardiseases, the regulation of platelet formation offers a unique aspectfor studying the blood compatibility of nanomaterials. In this study,the effects of SiO2 NPs with four sizes (80, 120, 200,and 400 nm) were investigated on the maturation and differentiationof the megakaryocytes into platelets. The results showed that SiO2 NPs promoted megakaryocyte development as manifested by theoccurrence of irregular cell morphology, enlargement of cell size,increases in DNA content and DNA ploidy, and formation of spore-likeprotrusions. The expression of megakaryocyte-specific antigen (CD41a)was up-regulated, due to SiO2 NP treatments. The correlationanalysis of SiO2 NP size with the above test bioindicatorsshowed that the smaller the SiO2 NPs were, the strongereffects they induced. Moreover, exposure to SiO2 NPs inducedthe up-regulation of both GATA-1 and FLI-1, while the transcriptional expressions of aNF-E2 and fNF-E2 remained unchanged. The significantpositive correlation of GATA-1 and FLI-1 with megakaryocytic maturation and differentiation suggested theircrucial roles in the SiO2 NP-promoted effect. The findingherein provided new insight into the potential health risk of SiO2 NPs by perturbing the platelet-involved hematological homeostasis.

Automated summary

The study found that SiO2 nanoparticles can promote the maturation and differentiation of megakaryocytes into platelets, and the effect of SiO2 nanoparticles is positively correlated with their size. This effect of SiO2 nanoparticles may be mediated by the upregulation of GATA-1 and FLI-1 gene expression. This finding provides new insight into the potential health risk of SiO2 nanoparticles by perturbing the platelet-involved hematological homeostasis.