Assessment of cancer-related signaling pathways in responses to polystyrene nanoplastics via a kidney-testis microfluidic platform (KTP).

ABSTRACT

As a new type of environmental pollutants, micro/nano plastics (MPs/NPs) derived from plastic products are commonly contact in daily life and lead to some serious health issues. The toxicity effects of MPs/NPs on the human body have aroused wide concerns. Although MPs/NPs have been reported to be transmitted into the kidney and reproductive organs, the molecular mechanisms of MPs/NPs toxicity remain unclear due to the lack of a physiologically relevant organ-organ linking platform in vitro. Here, we present a kidney-testis microfluidic platform (KTP) with NPs exposure that enables the communication of kidney and testis chambers and reproduces endothelium-linked chambers to simulate the state in vivo. The function of KTP was assessed by cell counting kit (CCK-8), tight junction protein claudin-2 and glucose consumption. Results revealed that MPs/NPs entered the kidney and testis via endocytosis. Immunofluorescence and ELISA analysis were performed on KTP at 200 µg/mL PS-NP to identify the dysregulated proteins on cancer-related signaling pathways, including the MAPK signaling pathway (RTK, RAS, ERK, JNK, P38, NRF2, TNF-α, and TNF-α-R) and the PI3K-AKT signaling pathway (PI3K, AKT, MDM2, P53, and ΒΑD). This multi-organ platform (KTP) contributes to clarifying cancer pathways triggered by MPs/NPs exposure and provides a promising method for assessing diseases induced by environmental pollutants.