HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation

Histone deacetylase 6 (HDAC6) is primarily a cytoplasmic enzyme that plays a crucial role in various biological processes, exerting both deacetylation-dependent and independent effects on numerous target molecules. This has led to the development of isoform-specific enzyme inhibitors. Renal transplantation (RT) is one of the preferred and cost-effective treatments for most patients with end-stage renal disease (ESRD). Recent studies have shown increased expression and activity of HDAC6 in kidney diseases.

Extensive research has established HDAC6 as a key modulator of both innate and adaptive immunity, prompting the development of HDAC6 inhibitors (HDAC6i) for various immune-related conditions. These inhibitors hold promise as therapeutic candidates for managing a range of renal diseases. Evidence suggests that HDAC6i can significantly protect against oxidative stress-induced damage, promote tolerance-related immune cell generation, and reduce fibrosis by inhibiting several profibrotic signaling pathways.

We propose that targeting HDAC6 could be a novel therapeutic strategy for addressing complications related to renal transplantation. This includes managing ischemia-reperfusion injury, inducing immune tolerance in transplants, balancing rejection responses, and improving chronic renal graft interstitial fibrosis. In this article, we will discuss the unique functions of HDAC6, highlighting its therapeutic mechanisms related to immunological processes and ACY-775 its promising potential for clinical application.