Plasminogen activator inhibitor-2 regulates immune response in kidney injury and renal aging mpact of plasminogen activator inhibitor-2 in kidney injury and renal aging

The plasminogen activator inhibitor-2 (PAI-2; encoded by the SerpinB2 gene) has been described in the context of macrophage activation and in cellular senescence. As both mechanisms are important in kidney disease we tested a possible role of PAI-2 in renal injury and repair. Methods:Aging, ischemia/reperfusion injury and unilateral ureteral obstruction were performed on the mice. Bone marrow was transplantefrom SerpinB2-/- to wild-type littermates and vice versa. Primary tubular cells and macrophages from SerpinB2-/- and wildtype mice were used for functional studies and transcriptional profiling. Results: PAI-2 expression was up-regulated in cultured senescent tubular cells and in kidneys of aged mice. In the lack of PAI-2 in SerpinB2-/- mice was associated with enhanced renal fibrosis and an inflammatory phenotype during aging and in kidney injury models. While acute injury was associated with fewer monocytes/macrophages in SerpinB2-/- kidneys the subsequent resolution of inflammation seen in wildtype kidneys was lacking in knockout mice. Conclusion: PAI-2 regulates renal aging, tubular damage, and resolution of inflammation. PAI-2 is crucial for kidney repair in mice . PMA treated wildtype and SerpinB2 -/- primary tubular cells