| First Author | Nath KA | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | Volume | 317 |
| Issue | 3 | Pages | F695-F704 |
| PubMed ID | 31215802 | Mgi Jnum | J:284407 |
| Mgi Id | MGI:6381082 | Doi | 10.1152/ajprenal.00085.2019 |
| Citation | Nath KA, et al. (2019) Heme oxygenase-2 protects against ischemic acute kidney injury: influence of age and sex. Am J Physiol Renal Physiol 317(3):F695-F704 |
| abstractText | Heme oxygenase (HO) activity is exhibited by inducible (HO-1) and constitutive (HO-2) proteins. HO-1 protects against ischemic and nephrotoxic acute kidney injury (AKI). We have previously demonstrated that HO-2 protects against heme protein-induced AKI. The present 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 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, on day 2 after ischemia, such deficiency augmented upregulation of injury-related genes and worsened histological 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 exacerbation of deficiency of HO-2 protein and HO activity may reflect phosphorylated STAT3, as activation of this proinflammatory transcription factor was accentuated early after ischemia in aged male HO-2(-/-) mice. This exacerbation may not reflect impaired induction of nephroprotectant genes, since the induction of HO-1, sirtuin 1, and beta-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 suppression of phosphorylated STAT3-dependent signaling. |
