Hcar1, short for hydroxycarboxylic acid receptor 1, is a G-coupled protein receptor (GPCR) of class A coupled to Gαi. It acts as the sole receptor for lactate, reducing cellular cAMP along with downstream Gβγ signaling. HCAR1 is involved in diverse biological processes such as neural activities, angiogenesis, inflammation, and metabolism [3].

In neonatal hypoxia-ischemia mouse models, HCAR1 knockout (KO) mice showed reduced tissue regeneration, impaired proliferation of neural progenitor and glial cells, and microglial activation compared to wild-type mice. Transcriptome analysis revealed a strong transcriptional response to HI in wild-type mice, while KO mice had a modest response, with dysregulation of cell cycle and innate immunity processes, suggesting HCAR1 is a key transcriptional regulator for post-HI tissue regeneration [1]. In colorectal cancer mouse models, ablation of Hcar1 decreased the recruitment of immunosuppressive CCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), enhanced CD8+ T cell activation, and reduced tumor burden, indicating HCAR1-mediated immunosuppression in cancer [2]. Also, HCAR1 KO mice manifested autistic-like behavior, suggesting its role in preventing such behaviors [4].

In conclusion, HCAR1 is crucial in multiple biological processes. Through gene knockout mouse models, its role in diseases like neonatal hypoxia-ischemia, colorectal cancer, and autism-related behaviors has been revealed. These findings enhance our understanding of the biological functions of HCAR1 and may provide new directions for disease treatment and prevention.