Work

Ngf/TrKA signal is associated with macrophage activation of acute kidney injury in mice

Year: 2025

Type: article

Abstract: To further clarify the molecular mechanisms of acute kidney injury (AKI), we analyzed the differential genes of AKI using second-generation sequencing. Enrichment of ferroptosis, apoptosis, and regulation of adaptive immune response pathways in both lipopolysaccharides (LPSs) and ischemia-reperfusion injury induced AKI mouse models. Twelve genes involving cell death were further identified in the STRING database. Real-time PCR and Western blotting were used to evaluate the associated biological expression of the differential genes. Real-time PCR analysis showed that the mRNA expression of nerve growth factor (Ngf) was upregulated in both the models. Multispectral immunofluorescence analysis showed that CD86 was co-expressed with Ngf. To elucidate the immunomodulatory role of Ngf in AKI, we established a murine macrophage model using clodronate liposome injection. We then used LPS injections to observe macrophage activation in mice. Compared to the normal control, colocalization of Ngf and CD86 increased in the renal tissue of mice after LPS injection, whereas macrophage clearance significantly impaired the colocalization of Ngf and CD86 in murine kidneys after LPS injection. Western blotting further showed upregulation of Ngf, TrKA, phosphorylated NF-κB p65, and NF-κB p65 in bone marrow-derived macrophages following LPS injection. In conclusion, our findings revealed that Ngf/TrKA signaling could be associated with macrophage activation in AKI, suggesting a novel potential therapeutic target for AKI.

Source: Renal Failure

DOI: 10.1080/0886022x.2025.2555687