Endogenous hepcidin synthesis protects the distal nephron against hemin and hemoglobin mediated necroptosis.

ABSTRACT: Hemoglobinuria is associated with kidney injury in various hemolytic pathologies. Currently, there is no treatment available and its pathophysiology is not completely understood. Here we studied the potential detrimental effects of hemoglobin (Hb) exposure to the distal nephron (DN). Involvement of the DN in Hb kidney injury was suggested by the induction of renal hepcidin synthesis (p < 0.001) in mice repeatedly injected with intravenous Hb. Moreover, the hepcidin induction was associated with a decline in urinary kidney injury markers 24p3/NGAL and KIM1, suggesting a role for hepcidin in protection against Hb kidney injury. We demonstrated that uptake of Hb in the mouse cortical collecting duct cells (mCCD_cl1) is mediated by multi-protein ligand receptor 24p3R, as indicated by

SUBMITTER: van Swelm RPL 

PROVIDER: S-EPMC5945780 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature