GATA6, short for GATA binding protein 6, is a zinc-finger transcriptional regulator in the GATA family. It plays key roles in cell fate determination, proliferation, migration, and organogenesis of endoderm-and mesoderm-derived organs in vertebrates. It is involved in multiple biological processes such as liver development [4], and is associated with various disease-related pathways [1,2,3,5,6]. Genetic mouse models are valuable for studying its functions.

In arterial calcification, knockdown of GATA6 via recombinant adeno-associated virus carrying GATA6 shRNA inhibited the development of arterial calcification in mice with chronic kidney disease (CKD). GATA6 accelerates vascular smooth muscle cell (VSMC) senescence-related arterial calcification by counteracting the anti-aging factor SIRT6 and impeding DNA damage repair [1].

In pancreatic cancer, GATA6 expression can distinguish classical and basal-like subtypes. The basal-like subtype, identified by lower GATA6 expression, is more chemoresistant [2].

In non-small cell lung cancer, down-regulation of GATA6, mediated by miR-196b-5p, promotes tumor progression [3].

In pulmonary arterial hypertension, GATA6 deficiency in pulmonary endothelial and smooth muscle cells is responsible for hyper-proliferative cellular phenotypes, vascular remodeling, and hypertension. Treatment with dimethyl fumarate, which resolves oxidative stress and BMPR deficiency related to GATA6 loss, shows potential therapeutic effects [6].

In conclusion, GATA6 is crucial for normal development and is involved in multiple disease processes. Gene-knockout or conditional-knockout mouse models have significantly contributed to understanding its role in arterial calcification, pancreatic cancer, non-small cell lung cancer, and pulmonary arterial hypertension. These studies provide potential new targets for intervention in related diseases.