Microplastics Exposure Causes the Growth Hormone Resistance on the Stem Cell

Abstract

With the large range of applications for plastic products, the potential hazards of polystyrene microplastics (PS-MPs) as a hazardous substance have been widely concerned. Mesenchymal stem cells (MSCs) are important cells in the body with high self-renewal ability, multidirectional differentiation potential and low immunogenicity. Growth hormone (GH) has important biological regulatory effects on MSCs. However, the toxicological effects of PS-MPs on the role of GH in hMSCs are unclear yet. In this work, we explored the effects of PS-MPs on the biological activity of GH in hMSCs. Initially, we conducted experiments to investigate the cellular behavior of GH in hMSCs. It is noteworthy that poststimulation with PS-MPs, there was a significant reduction in the quantity of GH entering the cytoplasm, with almost negligible distribution observed in the cell nucleus. Consequently, we proceeded to examine the GH/GHR-mediated signaling pathways. The data revealed that poststimulation with PS-MPs, the downstream signaling pathways, including JAK2-STATs1/3/5, were significantly downregulated. To elucidate this intriguing finding, we delved further into the molecular mechanisms underlying the desensitization of GH/GHR signaling induced by PS-MPs. Experimental data demonstrated that the entry of PS-MPs into the cells resulted in a significant increase in intracellular reactive oxygen species (ROS), leading to cellular senescence. In summary, PS-MPs may induce desensitization of GH signaling in hMSCs through the ROS-induced cellular senescence. This study provides crucial insights into the biological effects of PS-MPs on the GH bioactivity in hMSCs.