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.