Trichloroethylene-Mediated Abnormal GOLPH3 Expression Interferes with Autophagic Flux and Regulates Lysosomal Acidity and Function Activity in HK-2 Cells

Abstract Trichloroethylene (TCE), a widespread environmental and occupational hazardous chemical, exerts potent nephrotoxic effects, while its specific molecular mechanism remains largely elusive. In this investigation, we revealed that the exposure of HK-2 cells to environmentally relevant concentrations of TCE resulted in a significantly enhanced expression of Golgi phosphoprotein 3 (GOLPH3). Meanwhile, TCE treatment could significantly hinder the autophagic flux of HK-2 cells. Further, TCE exposure significantly reduced intracellular lysosomal acidity and impaired their functional activity. Notably, genetic silencing of GOLPH3 via RNA interference (RNAi) strategy effectively relieved autophagic obstruction and restored lysosomal acidity and function activity. In summary, this study indicates that TCE can induce severe autophagic flux disturbance and lysosomal acidity and function activity in HK-2 cells, in which GOLPH3 plays a key regulatory role and is expected to serve as a potential biomarker and intervention target for TCE-induced nephrotoxic damage.