Renal ischemia/reperfusion (IR) is associated with activation of the coagulation system and accumulation of blood clotting factors in the kidney. The aim of the present study was to examine the functional impact of Fibrinogen on renal inflammation, damage and repair in the context of IR injury. In this study, we found that IR was associated with a significant increase in renal deposition of circulating Fibrinogen. In parallel, IR-stress induced de novo expression of Fibrinogen in tubular epithelial cells as reflected by RT-PCR, immunofluorescence and in situ hybridization. In vitro, Fibrinogen expression was induced by Oncostatin-M and Hyper-IL-6 in primary tubular epithelial cells and Fibrinogen containing medium had an inhibitory effect on tubular epithelial cell adhesion and migration. Fibrinogen+/- mice showed similar survival as wild-type mice but better preservation in early postischemic renal function. In Fibrinogen-/- mice renal function and survival were significantly worse than in Fibrinogen+/- mice. Renal transplant experiments revealed reduced expression of tubular damage markers and attenuated proinflammatory cytokine expression but increased inflammatory cell infiltrates and TGF-β expression in Fibrinogen-/- isografts. These data point to heterogeneous effects of Fibrinogen in renal IR injury. While a complete lack of Fibrinogen may be detrimental, partial reduction of Fibrinogen in heterozygous mice can improve renal function and overall outcome.
- tubular expression
- Copyright © 2012, American Journal of Physiology - Renal Physiology