Lead exposure aggravates calcium oxalate crystal-induced renal injury and inflammation by upregulating IRF7 and promoting M1 macrophage polarization.

BACKGROUND

Calcium oxalate (CaOx) crystals, a major component of human nephrocalcinosis, induce inflammation and damage to renal tubular epithelial cells. Lead (Pb) is an environmental pollutant that is highly toxic to the kidneys and has not been studied in nephrocalcinosis research. Here, we investigated the role of Pb exposure in CaOx-induced renal injury and elucidated the underlying mechanisms.

METHODS

A mouse model of nephrocalcinosis was established by intraperitoneal injection of glyoxylate, and a renal injury model of renal tubular epithelial cells was established using calcium oxalate monohydrate. Crystal deposition and renal tissue damage were assessed by hematoxylin-eosin staining and PAS staining. Renal inflammation markers, including MCP-1, TNF-α, and IL-6, were analyzed by RT-PCR. WB analysis evaluated the protein expression levels of KIM-1, p-P65, and cleaved-IL-1β in tubular epithelial cells. In addition, we knocked down IRF7 (interferon regulatory factor 7) to clarify the role of IRF7 in Pb exposure and calcium oxalate crystal-induced kidney injury, and further evaluated the functional role of CCL3 in macrophage polarization.

RESULTS

This study suggested that Pb exposure exacerbated COM-induced HK-2 cell injury and inflammatory response. Similarly, in vivo, Pb exposure aggravated CaOx-induced renal injury and crystal deposition. In addition, silencing of IRF7 partially attenuated renal injury and reduced the expression levels of inflammatory factors, and silencing of CCL3 can alleviate M1 macrophage polarization.

CONCLUSION

Our results suggested that Pb exposure can aggravate CaOx-induced renal injury and inflammatory response by regulating IRF7 expression and M1 macrophage polarization. This provided new perspectives for the prevention and treatment of nephrocalcinosis.