**9. Clinical Applications**

Manipulation of HO-1 expression/activity for potential therapeutic strategies has already been explored. HO-1 may be activated through a wide range of both naturally occurring and chemically synthesized compounds. The most widely used HO-1 inducers/inducers are metalloporphyrins (MPs). These are all heme analogues that differ mainly in the metal moiety of the porphyrin structure. However, numerous other naturally occurring compounds have been reported to induce HO-1, including curcumin, resveratrol, quercentin, carnosic acid, carnosol and anthocyanin [83]. Both MPs, as well as all of the other naturally occurring compounds, have been proposed for their use in the treatments of various immune-mediated diseases, including kidney disease [84] as well as other immunemediated diseases, such as multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, lupus and inflammatory bowel disease [83]. The therapeutic potential of HO-1 has also been highlighted by other studies that have proposed the potential use of MPs with nonimmune-mediated forms of disease, such as non-alcoholic fatty liver disease [85]. Finally, manipulation of the HO reaction has also enabled research towards potential therapeutic strategies via CO release via CO-releasing molecule (CORM) administration in preclinical models of type 1 diabetes [86] and in MS [87,88], as well as in models of autoimmune hepatitis [89].

#### **10. Conclusions**

Apart from its established role as a strong antioxidant and anti-apoptotic enzyme, HO-1 is by now also recognized as an important modulator of various immune pathways and responses. Furthermore, its increased inducibility through multiple varied types of inducers renders it a highly interesting target for novel therapeutic strategies against immune-mediated diseases, including kidney disease. Further research is needed, in order to unravel the exact mechanisms of immunomodulation in kidney disease, which will enable translation into innovative treatment strategies against immune-mediated kidney disease.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

