Fibrinogen-like protein 2-complement C3 interaction exacerbates tubular inflammation in acute kidney injury by elevating complement C3a levels.

چکیده اصلی

Renal tubular epithelial cells are among the earliest renal parenchymal cells to be injured in the context of acute kidney injury (AKI). Numerous studies have confirmed that fibrinogen-like protein 2 (FGL2) can regulate the occurrence and development of inflammation during disease progression. We found that FGL2 expression is elevated under AKI conditions. However, the role of FGL2 in AKI remains unclear. To elucidate the role of FGL2 in AKI, we employed lentiviral and adeno-associated virus for transfection in cellular and murine models. Furthermore, by leveraging datasets from the gene expression omnibus and gene set enrichment analysis databases, we identified the inflammation-related genes in AKI and predicted their interaction with FGL2. Both in vivo and in vitro studies showed that overexpression of FGL2 markedly increased complement C3a (C3a) levels and exacerbated inflammation and injury. In contrast, knockdown of FGL2 resulted in a marked decline in C3a levels, which not only conferred a substantial protective effect against hypoxia/reoxygenation-induced injury in tubular cells but also effectively alleviated kidney injury in mice. At the molecular level, FGL2 interacts with complement C3, leading to elevated C3a production. This stimulates the inflammatory response of renal tubular epithelial cells, thereby inducing tubular damage. Targeting FGL2 may hold potential prevention and treatment strategy for tubular injury in AKI.

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