Hdac3, short for Histone deacetylase 3, is an important epigenetic modifying enzyme. It can affect chromatin structure and transcriptional regulation by deacetylating histones and non-histones proteins, playing various roles in biological processes [2,5]. It is involved in multiple pathways, such as the cGAS-STING pathway in microglia [3].

In mouse models, Hdac3 deficiency has shown diverse effects. In type II alveolar epithelial cells, Hdac3 conditional knockout (Sftpc-cre; Hdac3f/f) alleviated sepsis-induced acute lung injury by preserving mitochondrial quality control via the FOXO1-ROCK1 axis [2]. In microglia, Hdac3 knockout (HDAC3-miKO) ameliorated post-stroke long-term functional and histological outcomes by specifically inhibiting the proliferation of pro-inflammatory microglia [1]. Also, deletion of Hdac3 in microglia attenuated ischemia/reperfusion-induced neuroinflammation and brain injury by regulating the microglial cGAS-STING pathway [3]. In the context of renal diseases, genetic Hdac3 knockout mitigated GPX4 suppression, ferroptosis, and fibrosis-associated renal functional loss in AKI-CKD mouse models [4].

In conclusion, Hdac3 is crucial in regulating various biological processes. Studies using Hdac3 knockout or conditional knockout mouse models have revealed its significant roles in diseases like ischemic stroke, acute lung injury, cerebral ischemia/reperfusion, and AKI-CKD progression. These models have provided valuable insights into the underlying mechanisms, offering potential therapeutic targets for these diseases.