The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Abstract

The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.