To investigate whether urokinase-type plasminogen activator receptor (uPAR) affected renal interstitial fibrosis and angiogenesis induced by renal unilateral ischemia-reperfusion injury (uIRI) in mice.

Female wild-type (WT) mice and uPAR-knockout (uPAR-ko) mice aged 8-10 weeks with C57BL/6J background were selected to construct the renal uIRI model. The experimental mice were divided into four groups: wild-type sham operation group (WT sham group), WT uIRI group, uPAR-ko sham group, and uPAR-ko uIRI group, with five mice in each group. The mice were sampled on days 1, 3, and 14 after modeling to detect serum creatinine, blood urea nitrogen, and renal histopathological changes. Sirius red staining was used to detect collagen deposition area in renal tissues. Western blotting, RT-qPCR, and immunohistochemistry were used to detect the expression of type Ⅰ collagen, vimentin, E-cadherin, α-smooth muscle actin, and endomucin in renal tissues. Immunofluorescence was used to detect the expression of CD31, a marker of angiogenesis, in renal tissues. Statistical comparisons between groups were performed using the two-way analysis of variance.

Compared with the WT sham group and the uPAR-ko sham group, respectively, the WT uIRI group and the uPAR-ko uIRI group showed higher levels of serum creatinine, blood urea nitrogen, and renal tubular injury scores at both 1 day and 3 days after modeling (all P< 0.05). Compared with the WT uIRI group, the uPAR-ko uIRI group exhibited higher levels of serum creatinine, blood urea nitrogen, and renal tubular injury scores at both 1 day and 3 days after modeling, but lower level of blood urea nitrogen at 14 days after modeling (all P<0.05). Compared with the WT sham group and the uPAR-ko sham group, respectively, after 14 days of modeling, the WT uIRI group and the uPAR-ko uIRI group exhibited higher levels of renal tissue collagen area, and higher levels of mRNA and protein expressions of type I collagen, vimentin, and α-smooth muscle actin, but lower levels of protein expressions of E-cadherin, endomucin, and CD31 (all P< 0.05). Compared with the WT uIRI group, the uPAR-ko uIRI group displayed higher level of renal tissue collagen area, and higher levels of protein and mRNA expressions of type I collagen, vimentin, and α-smooth muscle actin, while the protein expressions of E-cadherin, endothelial cadherin, and CD31 were lower (all P< 0.05).

The deficiency of uPAR could exacerbate the kidney dysfunction and renal interstitial fibrosis induced by uIRI, as well as reduced renal angiogenesis in mice.