HO-1 mitigates acute kidney injury and subsequent kidney-lung cross-talk

Abstract

Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). IRI-induced AKI releases proinflammatory cytokines (e.g. IL-1β, TNF-α, IL-6) that induce a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage. AKI is associated with poor outcomes, particularly when extrarenal complications or distant organ injuries occur. Acute lung injury (ALI) is a major remote organ dysfunction associated with AKI. Hence, kidney-lung cross-talk remains a clinical challenge, especially in critically ill population. The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against renal IRI and may be preventively induced using hemin prior to renal insult. However, the use of hemin-induced HO-1 to prevent AKI-induced ALI remains poorly investigated. Mice received an intraperitoneal injection of hemin or sterile saline 1 day prior to surgery. Twenty-four hours later, mice underwent bilateral renal IRI for 26 min or sham surgery. After 4 or 24 h of reperfusion, mice were sacrificed. Hemin-induced HO-1 improved renal outcomes after IRI (i.e. fewer renal damage, renal inflammation, and oxidative stress). This protective effect was associated with a dampened systemic inflammation (i.e. IL-6 and KC). Subsequently, mitigated lung inflammation was found in hemin-treated mice (i.e. neutrophils influx and lung KC). The present study demonstrates that hemin-induced HO-1 controls the magnitude of renal IRI and the subsequent AKI-induced ALI. Therefore, targeting HO-1 represents a promising approach to prevent the impact of renal IRI on distant organs, such as lung.

Keywords:

• Acute kidney injury
• acute lung injury
• cross-talk
• heme oxygenase-1
• hemin
• renal ischemia-reperfusion
• word count

Acknowledgments

The authors thank Eric Deprez (Laboratory of Experimental Nephrology, Université Libre de Bruxelles, Brussels, Belgium) for technical assistance.

Disclosure statement

The authors of this manuscript have no conflict of interest to disclose as described by Free Radical Research.

Additional information

Funding

This work was supported by grants from the “Fonds de la Recherche Scientifique Médicale” (FRSM) to Maxime Rossi and Jean-Michel Hougardy, the “Fonds Erasme pour la Recherche Médicale” to Jean-Michel Hougardy, and the “Société Belge d’Urologie” (SBU) to Maxime Rossi.