Htr2a, also known as 5-Hydroxytryptamine receptor 2A, is a key serotonin receptor. It serves as a central regulator in fetal brain development and adult cognitive function. Serotonin, the ligand of Htr2a, is involved in numerous physiological processes, and Htr2a activation is associated with the Gq-coupled signaling pathway, which can lead to various downstream effects [2,3,5]. Htr2a has been implicated in many neuropsychiatric phenotypes and other diseases, highlighting its overall biological importance [3,4].

In a papain-induced lung inflammation mouse model, Il5cre/+·Htr2aflox/flox mice with ILC2-specific depletion of Htr2A abolished the inhibitory effect of the HTR2A selective agonist (DOI) on ILC2s. This indicates that Htr2a on ST2+ ILC2s plays a role in the type 2 lung immune response, and targeting it could be a treatment strategy for type 2 lung inflammation [1]. In neonatal rat cardiomyocytes, knockdown of Htr2a using shRNA repressed isoproterenol (ISO)-induced cardiomyocyte hypertrophy, while overexpression promoted it. This shows that Htr2a promotes cardiac hypertrophy through activating the PI3K-PDK1-AKT-mTOR signaling pathway [2].

In conclusion, Htr2a is crucial for normal brain development and cognitive function. Through gene-knockout (KO) or conditional-knockout (CKO) mouse models, it has been revealed to be involved in type 2 lung inflammation and cardiac hypertrophy. Understanding Htr2a's function in these disease areas can potentially lead to new therapeutic strategies for related diseases. [1,2]

References:

1. Wang, Zhishuo, Yan, Chenghua, Du, Qizhen, Zhu, Jinfang, Sun, Bing. 2023. HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation. In Cellular & molecular immunology, 20, 404-418. doi:10.1038/s41423-023-00982-6. https://pubmed.ncbi.nlm.nih.gov/36823235/

2. Gao, Weinian, Guo, Na, Zhao, Shuguang, Liao, Hongjuan, Chi, Kui. 2020. HTR2A promotes the development of cardiac hypertrophy by activating PI3K-PDK1-AKT-mTOR signaling. In Cell stress & chaperones, 25, 899-908. doi:10.1007/s12192-020-01124-x. https://pubmed.ncbi.nlm.nih.gov/32519137/

3. Norton, Nadine, Owen, Michael J. . HTR2A: association and expression studies in neuropsychiatric genetics. In Annals of medicine, 37, 121-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16026119/

4. Serretti, Alessandro, Drago, Antonio, De Ronchi, Diana. . HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. In Current medicinal chemistry, 14, 2053-69. doi:. https://pubmed.ncbi.nlm.nih.gov/17691947/

5. Paquette, Alison G, Marsit, Carmen J. . The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes. In Journal of cellular biochemistry, 115, 2065-72. doi:10.1002/jcb.24883. https://pubmed.ncbi.nlm.nih.gov/25043477/