Hdac5, a member of the class IIa family of histone deacetylases, plays crucial roles in various biological processes. It is involved in gene expression regulation by modifying histone acetylation levels. Hdac5 is associated with multiple pathways, such as TGF-β signaling, NF-κB signaling, and PI3K/Akt signaling, which are essential for normal cellular functions and are often dysregulated in diseases. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In hypertrophic scar formation, depletion of Hdac5 in vivo attenuated HS formation and inhibited fibroblast activation in vitro. Hdac5 interacted with MEF2A to suppress Smad7 expression, and its deficiency led to decreased Smad2/3 phosphorylation [1]. In pancreatic cancer, Hdac5 downregulation was associated with favorable prognosis. It regulated PD-L1 expression by interacting with NF-κB p65, and its silencing or inhibition sensitized tumors to immune checkpoint blockade therapy [2]. In diabetic kidney disease, knockdown of Hdac5 in HK2 cells ameliorated high glucose-induced epithelial-mesenchymal transition via downregulating TGF-β1, and its expression was regulated by the PI3K/Akt signaling pathway [3].

In conclusion, Hdac5 is vital in regulating multiple biological processes and is implicated in various disease conditions. Findings from gene knockout models have provided insights into its roles in fibrotic diseases, cancer, and diabetic kidney disease, highlighting its potential as a therapeutic target for these diseases.