Table 1.
The beneficial effects of HO-1 and its products in AKI
| Genetic manipulation | Phenotype | Model | Effect | Reference |
|---|---|---|---|---|
| HO-1-/- | Global HO-1 deficiency | Mouse renal IR | Increased MCP-1, IL-6 and reduced IL-10 | [36,49] |
| HO-1-/- | Global HO-1 deficiency | Mouse UUO | Increased MCP-1, IL-6 and reduced IL-10 | [50] |
| Ad-HO-1 | HO-1 overexpression in kidney | Rat renal IR | Preserved renal function | [10] |
| HO-1-/- | Global HO-1 deficiency | Mouse cisplatin nephrotoxicity | Worse renal structural and functional injury | [95] |
| HO-1 overexpression | Global HO-1 overexpression | Mouse cisplatin nephrotoxicity, rhabdomyolysis | Preserved renal structure and function | [96] |
| PT-HO-1-/- | Proximal tubule HO-1 deletion | Mouse cisplatin nephrotoxicity | Exacerbated renal structure and function | [97] |
| PT-HO-1 overexpression | Proximal tubule HO-1 overexpression | Mouse cisplatin nephrotoxicity | Preserved renal structure and function | [97] |
| Ad-HO-d1 | HO-1 overexpressing BMDM | LPS/IFN injury | Increased IL-10-1 and reduced TNF-α and NO | [47] |
| Myeloid HO-1-/- | Deletion of HO-1 only in myeloid cells | Mouse renal IR | Egress of renal dendritic cells to lymph node for antigen presentation | [49] |
| GFP+HO-1-/- | Global GFP expressing HO-1 deficient mouse | Mouse syngeneic kidney transplant | Egress of donor renal dendritic cells to lymph node for antigen presentation | [49] |
| HO-1 overexpressing HEK293 | Overexpression of HO-1 | Human renal epithelial cells | Inhibits ROS generation, autophagy, and apoptosis and promotes cell survival during oxidative stress | [84] |
| HO-1 overexpressing proximal tubular cells | Overexpression of HO-1 in primary HO-1-/- PTC | Mouse PTC: hypoxia | Inhibits apoptosis and promotes cell survival during hypoxic stress | [98] |
| Mitochondrial HO-1 | Overexpression of HO-1 in mitochondria | Human renal epithelial cells | Inhibits ROS generation and apoptosis following hypoxia and oxidative stress | [98] |
| Gunn rat | Increased bilirubin | Rat hyperoxia | Increased resistance to free radical injury | [99] |
| Acute cholestatic liver disease | Increased bilirubin | Rat rhabdomyolysis | Protects against rhabdomyolysis injury | [100] |
Reproduced with permission from the American Journal of Kidney Diseases and Bolisetty et al Am J Kidney Dis 2017;69:531-545 [1].
AKI, acute kidney injury; BMDM, bone marrow-derived MΦ; GFP, green fluorescent protein; HO-1, heme oxygenase-1; IFN, interferon; IR, ischemia/reperfusion; LPS, lipopolysaccharide; PTC, proximal tubular cell; ROS, reactive oxygen species; UUO, unilateral ureteral obstruction.