Heme Oxygenase-2 Protects Against Ischemic Acute Kidney Injury: The Influence of Age and Sex.

This study examined whether HO-2 is protective in ischemic AKI. Renal ischemia was imposed on young and aged HO-2+/+ and HO-2-/- mice. On days 1 and 2 after renal ischemia, there were no significant differences in renal function either between young male HO-2+/+ and HO-2-/- mice, between young female HO-2+/+ and HO-2-/- mice, or between aged female HO-2+/+ and HO-2-/- mice. However, in aged male mice, HO-2 deficiency worsened renal function on days 1 and 2 after ischemic AKI, and, at day 2 after ischemia, such deficiency augmented upregulation of injury-related genes and worsened histologic injury. Renal HO activity was markedly decreased in unstressed aged male HO-2-/- mice and remained so after ischemia, despite exaggerated HO-1 induction in HO-2-/- mice after ischemia. Such exacerbatory effects of deficiency of HO-2 protein and HO activity may reflect p-STAT3, as activation of this proinflammatory transcription factor was accentuated early after ischemia in aged male HO-2-/- mice. This exacerbatory effect may not reflect impaired induction of nephroprotectant genes, since the induction of HO-1, SIRT1 and β-catenin was accentuated in aged male HO-2-/- mice after ischemia. We conclude that aged male mice are hypersensitive to ischemic AKI, and that HO-2 mitigates such sensitivity. We speculate that this protective effect of HO-2 may be mediated, at least in part, by suppressing p-STAT3-dependent signaling. PMID: 31215802 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research