Article
Pathophysiological relevance of B Cell Activating Factor (BAFF) and BAFF Receptor (BAFF-R) for renal ischemia/reperfusion (I/R) injury
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Published: | August 30, 2023 |
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Introduction: Acute kidney injury (AKI) accompanies with high morbidity and mortality. Incomplete renal recovery can lead to chronic and finally end-stage kidney disease, which results in the requirement of lifelong dialysis or kidney transplantation. The B cell activating factor (BAFF), a cytokine of the tumor necrosis factor (TNF) family, plays an important role for activation, differentiation and survival of B cells. By supporting B cells, which in turn play an important role in inflammatory processes and the production of antibodies, BAFF is related to AKI, transplantation and graft rejection.
Methods: In order to investigate the impact of BAFF and its receptor BAFF-R on the development of AKI, we performed the well-established ischemia/reperfusion (I/R) model in BAFF (B6.129S2-Tnfsf13btm1Msc/J) and BAFF-R (B6(Cg)-Tnfrsf13ctm1Mass/J) deficient mice. To receive a first impression of the effect of BAFF and BAFF-R knockout, the transcriptome of the ischemic and contralateral control kidneys was analyzed and compared to the wildtype littermates.
Results: In ischemic kidneys, we detected the upregulation of the genes Lcn2, Lyz2, Cd44, Fn1 and Il1rn as well as the downregulation of Kl with different expression patterns in BAFF and BAFF-R knockout mice. Up- and downregulation of each investigated gene was higher in BAFF-R knockout and lower in BAFF knockout compared to wildtype littermates. Furthermore, Lysozyme 2 (Lyz2) expression was remarkable upregulated in ischemic kidneys in both strains.
Conclusion: Findings of this study lead to the assumption that BAFF knockout seems to have a positive effect, while BAFF-R knockout worsened I/R injury. In addition, our study shows for the first time a remarkable renal upregulation of Lyz2 in a murine I/R model. Therefore, Lyz2 can be a conceivable predictive or early biomarker in case of I/R and AKI.