Nanoplastic exposure induces mitochondrial dysfunction–driven inflammation and senescence in renal tubular epithelial cells

ABSTRACT: Nanoplastic (NP) particles are emerging environmental contaminants with increasing concern regarding their potential impacts on human health; however, their effects on kidney function remain poorly understood. Here, we combined in vivo and in vitro approaches to investigate renal toxicity induced by chronic NP exposure. Oral administration of NPs (200 mg/kg/day) to mice for six weeks resulted in tubular-specific kidney injury accompanied by inflammatory and fibrotic responses. Transcriptomic profiling revealed coordinated downregulation of mitochondrial oxidative phosphorylation–related genes along with enrichment of inflammatory and fibrotic pathways in the kidney. Consistently, NP exposure directly induced mitochondrial dysfunction in renal tubular epithelial cells, as evidenced by impaired oxidative phosphorylation, increased mitochondrial reactive oxygen species, and structural mitochondrial abnormalities. Mitochondrial damage was associated with activation of STING-dependent inflammatory signaling; pharmacological inhibition of STING attenuated inflammatory responses but did not suppress NP-induced cellular senescence, indicating mechanistic dissociation between inflammation and senescence. In contrast, prolonged NP exposure induced robust cellular senescence linked to sustained mitochondrial dysfunction. Activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) restored mitochondrial function and suppressed both inflammatory signaling and cellular senescence in vitro. Importantly, pharmacological activation of PGC1α in NP-exposed mice mitigated mitochondrial damage, renal inflammation, senescence, and fibrotic remodeling in vivo. Collectively, these findings identify mitochondrial dysfunction as a central driver of NP-induced renal inflammation and senescence and provide mechanistic insight into the hazardous effects of NP exposure on the kidney.

ORGANISM(S): Mus musculus

PROVIDER: GSE330110 | GEO | 2026/05/13

REPOSITORIES: GEO