Bst-1/CD157 Modulates Inflammation and Kidney Injury in Sepsis

Background: Bone marrow stromal cell antigen-1 (Bst-1), also known as CD157, is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein involved in a variety of biological processes. In our previous studies, we identified Bst-1 as a suppressive factor of renal fibrosis. We also demonstrated that Bst-1 knockout (KO) mice show reduced susceptibility to ischemia-reperfusion-induced acute kidney injury (AKI). However, the renal localization of Bst-1 and the mechanisms underlying its protective effects in AKI remain unclear. This study aimed to determine the cellular localization of Bst-1 in the kidney and to investigate its role in lipopolysaccharide (LPS)-induced AKI, a model of sepsis-associated kidney injury. Methods: Bst-1 KO mice and their wild-type (WT) littermates (8–12 weeks old) were intraperitoneally administered LPS (10 mg/kg). After 24 hours, systemic inflammation and kidney injury were assessed. To determine the localization of Bst-1, kidneys from 8-week-old WT mice were harvested, enzymatically dissociated into single-cell suspensions, and labeled with an anti-Bst-1 antibody. Bst-1-positive cells were isolated using fluorescence-activated cell sorting (FACS), followed by single-cell RNA sequencing (scRNA-seq) to identify cell types expressing Bst-1. Results: LPS administration caused a significant increase in plasma TNF-α levels in WT mice, indicating systemic inflammation, while this increase was attenuated in Bst-1 KO mice. Furthermore, WT mice exhibited elevated expression of kidney injury markers such as Ngal and Kim-1 following LPS challenge, consistent with the development of AKI. In contrast, Bst-1 KO mice showed reduced expression of these markers and less severe kidney injury. scRNA-seq analysis revealed that Bst-1 is expressed in vascular endothelial cells, a subset of tubular epithelial cells, and macrophages within the kidney. Conclusion: Bst-1 deficiency attenuates both systemic inflammation and kidney injury in an LPS-induced sepsis model. These protective effects may be mediated through Bst-1 expressed in vascular endothelial cells, certain tubular epithelial cells, and macrophages.