Dual roles of hydrogen peroxide in promoting zebrafish renal repair and regeneration.

Acute renal injury (AKI) is a serious disorder of renal failure or renal damage that occurs within hours or days. At present, there is no approved pharmaceutical treatment for AKI. Zebrafish is an excellent model for studying the repair of AKI because of its remarkable ability to repair kidney injury. Using zebrafish AKI model inducing by gentamicin, we found that hydrogen peroxide (HO) plays dual roles during the period of AKI recovery including renal repair and kidney regeneration. In the repair stage of AKI, HO was produced in proximal and distal segments of renal tubules. By inhibiting HO generation using Duox Vivo-Morpholino or chemical inhibitor, it was observed of severe damage of renal tubules, and extensive cell apoptosis. In the stage of regeneration, we found that HO was highly generated in renal interstitium. Inhibiting production of HO could significantly down-regulate the ability of kidney regeneration, which was associated with the failure of proliferation of renal progenitor cells. Therefore, HO acts as a protective factor in renal repair and an initial signal of kidney regeneration, indicating the key roles of HO in promoting recovery of AKI in zebrafish.