As one of the most common air pollutants, fine particulate matter (PM2.5) increases the risk of diseases in various systems, including the urinary system. In the present study, we exposed male and female C57BL/6J mice to PM2.5 for 8 weeks. Examination of renal function indices, including creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), and urinary microalbumin, indicated that the kidneys of female mice, not male mice, underwent early renal injury, exhibiting glomerular hyperfiltration. Meanwhile, pathological staining showed that the kidneys of female mice exhibited enlarged glomerulus that filled the entire Bowman's capsule in the female mice. Afterward, we explored the potential causes and mechanisms of glomerular hyperfiltration. Variations in mRNA levels of key genes involved in the renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) demonstrated that PM2.5 led to elevated glomerular capillary hydrostatic pressure in female mice by disturbing the balance between the RAS and KKS, which in turn increased the glomerular filtration rate (GFR). In addition, we found that PM2.5 increased blood glucose levels in the females, which enhanced tubular reabsorption of glucose, attenuated macular dense sensory signaling, induced renal hypoxia, and affected adenosine triphosphate (ATP) synthesis, thus attenuating tubuloglomerular feedback (TGF)-induced afferent arteriolar constriction and leading to glomerular hyperfiltration. In conclusion, this study indicated that PM2.5 induced glomerular hyperfiltration in female mice by affecting RAS/KKS imbalances, as well as the regulation of TGF; innovatively unveiled the association between PM2.5 subchronic exposure and early kidney injury and its gender dependence; enriched the toxicological evidence of PM2.5 and confirmed the importance of reducing ambient PM2.5 concentrations.
Keywords: PM2.5; kallikrein–kinin system; renal hyperfiltration; renin–angiotensin system; tubular reabsorption; tubuloglomerular feedback.