Htr7, also known as 5-hydroxytryptamine receptor 7, belongs to the G protein-coupled receptors (GPCRs) family. It is involved in multiple biological functions, such as regulating cell proliferation, immune responses, and itch sensations. The activation of Htr7 can trigger downstream signaling pathways, including the PI3K/AKT pathway [1].

In laryngeal cancer, Htr7 is significantly upregulated. Knockdown of Htr7 in cells and animal models inhibited laryngeal cancer proliferation and growth, indicating its role in promoting cancer growth through the activation of the PI3K/AKT pathway [1].

In a mouse model of atopic dermatitis, mice lacking Htr7 displayed reduced scratching and skin lesion severity, highlighting its role in acute and chronic itch [2].

In the gut, mouse enteric neurons control intestinal plasmacytoid dendritic cell function via the serotonin-Htr7 signaling axis, which regulates IgA induction and host defense against oral Salmonella Typhimurium infection [3].

In a lipopolysaccharide-induced neuroinflammation and cognitive impairment mouse model, Htr7+ Tregs transfected with lentivirus to knockdown Htr7 expression failed to alleviate neuroinflammation and cognitive impairment, suggesting that Htr7+ Tregs mitigate these conditions by suppressing CD8+ T cell infiltration and microglia activation [4].

In a water avoidance stress-induced visceral hypersensitivity IBS mouse model, miRNA-29a knockout led to overexpression of Htr7 and attenuated visceral hyperalgesia, indicating a role of Htr7 in this IBS-related symptom [5].

In goat mammary epithelial cells, treatment with a selective antagonist of 5-HTR7 rescued the inhibitory effect of 5-hydroxytryptophan on β-casein synthesis and pro-apoptotic effect, suggesting Htr7 mediates these impacts [6].

In conclusion, Htr7 is involved in various biological processes and disease conditions. The use of gene knockout or knockdown in mouse models has been crucial in revealing its functions in cancer growth, itch, immune responses in the gut, neuroinflammation, visceral hyperalgesia, and mammary gland-related processes. These findings provide potential therapeutic targets for treating laryngeal cancer, itch-related diseases, gut infections, neuroinflammation, IBS, and for improving milk quality.

References:

1. Sheng, Xiaoli, Liu, Wenlin, Lu, Zhongming, Liu, Tao, Zhang, Siyi. . HTR7 promotes laryngeal cancer growth through PI3K/AKT pathway activation. In Annals of translational medicine, 9, 840. doi:10.21037/atm-21-1069. https://pubmed.ncbi.nlm.nih.gov/34164474/

2. Morita, Takeshi, McClain, Shannan P, Batia, Lyn M, Brem, Rachel B, Bautista, Diana M. 2015. HTR7 Mediates Serotonergic Acute and Chronic Itch. In Neuron, 87, 124-38. doi:10.1016/j.neuron.2015.05.044. https://pubmed.ncbi.nlm.nih.gov/26074006/

3. Zhang, Hailong, Hasegawa, Yuko, Suzuki, Masataka, Jackson, Ruaidhrí P, Waldor, Matthew K. 2024. Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling. In Nature communications, 15, 9237. doi:10.1038/s41467-024-53545-2. https://pubmed.ncbi.nlm.nih.gov/39455564/

4. Xue, Dinghao, Guo, Xu, Liu, Jingjing, Wang, Long, Fu, Qiang. 2024. Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide. In Journal of neuroinflammation, 21, 241. doi:10.1186/s12974-024-03239-9. https://pubmed.ncbi.nlm.nih.gov/39334486/

5. Zhu, He, Xiao, Xi, Chai, Yuna, Yan, Xue, Tang, Hongmei. 2019. MiRNA-29a modulates visceral hyperalgesia in irritable bowel syndrome by targeting HTR7. In Biochemical and biophysical research communications, 511, 671-678. doi:10.1016/j.bbrc.2019.02.126. https://pubmed.ncbi.nlm.nih.gov/30827505/

6. Du, Wei, Zhang, Zhi Fei, Xiao, Jia Ying, Liu, Weng Yi, Zheng, Hui Ling. . 5-Hydroxytryptophan inhibits β-casein biosynthesis and promotes goat mammary epithelial cell apoptosis through the JAK2/STAT5a axis and the HTR7. In Journal of animal science, 101, . doi:10.1093/jas/skad089. https://pubmed.ncbi.nlm.nih.gov/36964762/