CLCF1 is up-regulated in renal ischemia reperfusion injury and may associate with FOXO3

BACKGROUND: Ischemia-reperfusion injury (IRI) is one of the most important risk factors for acute kidney injury. In kidney transplantation, renal IRI can induce delayed graft function (DGF). However, the mechanisms that link IRI to DGF remain unclear. This study aimed to find molecular markers of renal IRI which are also associated with DGF. METHODS: A previously constructed database of differentially expressed genes in a murine IRI model was compared with a published DGF database. The expression of cardiotrophin-like cytokine factor 1 (CLCF1) was detected using immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (qPCR) assays. Serum CLCF1 was measured using an enzyme-linked immunosorbent assay (ELISA), and serum creatinine (Cr) was tested to evaluate kidney function. RESULTS: By comparing the IRI database and the DGF database, we identified 107 differentially expressed genes, including 79 upregulated and 28 downregulated genes. CLCF1 was one of the upregulated genes found in the 2 databases. The levels of CLCF1 in IRI-treated kidney tissues and serum CLCF1 were upregulated compared to sham-operated mice. CLCF1 belongs to the interleukin-6 (IL-6) family, and the forkhead box O3 (FOXO3) gene plays a key role in regulating IL-6 expression. We observed that FOXO3 knockout induced an increase in serum CLCF1 levels in sham-operated mice. However, FOXO3 knockout failed to increase CLCF1 levels in IRI-treated mice. CONCLUSIONS: CLCF1 is upregulated in renal IRI and may be regulated by FOXO3. Our data indicated that CLCF1 might be a potential biomarker linking renal IRI to DGF in kidney transplantation.