Gata6, also known as GATA-binding protein 6, is a zinc-finger transcriptional regulator belonging to the GATA family. It plays key roles in cell fate determination, proliferation, migration, and organogenesis of endoderm-and mesoderm-derived organs. It is involved in various pathways such as those related to oxidative stress regulation in pulmonary arterial hypertension [8]. Genetic models, like KO/CKO 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 CKD mice. Gata6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting SIRT6 and impeding DNA damage repair [1].

In pancreatic cancer, Gata6 expression can distinguish classical and basal-like subtypes, with basal-like tumors being more chemoresistant. Gata6 expression was prognostic in a multivariate analysis [2].

In the heart, disruption of the pericardial cavity, where Gata6+ macrophages reside, accelerated maladaptive post-myocardial infarction cardiac remodeling. These macrophages relocate to the injured heart and prevent cardiac fibrosis [3].

In non-small cell lung cancer, down-regulation of Gata6, mediated by miR-196b-5p, promotes tumor progression [4].

Gata6 is a lineage-determining transcription factor of peritoneal resident macrophages, controlling their phenotypic and functional features [5].

In liver development, Gata6 is involved in multiple stages including endoderm liver-lineage determination [6].

In pancreatic cancer, while increased GATA6 expression can enhance cell growth, experimental evidence in genetic mouse models has also revealed a tumor-suppressive role, and its roles in pancreatic tumorigenesis remain to be fully defined [7].

In pulmonary arterial hypertension, Gata6 deficiency in pulmonary vascular cells leads to hyper-proliferative phenotypes, vascular remodeling, and hypertension. Gata6 acts as a positive regulator of anti-oxidant enzymes [8].

In conclusion, Gata6 is essential for normal development and function in multiple organs. Model-based research, especially using Gata6 KO/CKO mouse models, has revealed its roles in diseases such as arterial calcification, pancreatic cancer, non-small cell lung cancer, and pulmonary arterial hypertension, providing insights into disease mechanisms and potential therapeutic targets.