SerpinB2 inhibitor is a coagulation factor that inactivates urokinase and tPA. It is also a regular of inflammatory processes, as it can facilitate macrophage activation and cellular senescence. These mechanisms indicate that the SerpinB2 inhibitor could play a role in preventing and repairing renal aging and injury. This study aims to analyze the efficacy of SerpinB2 in regulating the immune response in kidney aging and injury.
In this study, SerpinB2 knockout mice were subjected to ischemia-reperfusion injury or unilateral ureteral obstruction. The researchers conducted phagocyte depletion to assess SerpinB2’s function beyond the effects of macrophages. The cell type-dependent effects were studied by transplanting bone marrow from knockout mice to wild-type mice. The primary outcome was successful kidney repair.
The kidneys of aged mice, cultured senescent tubular cells, and renal stress models demonstrated the upregulation of SerpinB2 expression. The lack of SerpinB2 had no effect on senescence markers in aged knockout mice but was associated with increased fibrosis and kidney damage. In stress models, inflammatory cell infiltration was lower initially but later increased. SerpinB2 tubular cells exhibited an attenuated expression of chemokine CCL2.
The findings suggested that SerpinB2 is needed for a successful repair, kidney homeostasis during aging, coordination, and resolution of inflammation.