Npsr1, which encodes the receptor for neuropeptide S (NPS), is involved in multiple physiological processes. The NPS-NPSR1 signaling is associated with anxiety, inflammation, and nociception [2]. It has been found to be part of various pathways such as calcium mobilization, cAMP/PKA, and MAPK/ERK signaling pathways in birds [4].

In inflammatory bowel disease (IBD), Npsr1 expression was elevated in the intestinal tissues of patients. Npsr1 knockdown in vitro and in DSS-induced mouse colitis models provided protection, reducing CD4+ T cell-mediated immune responses, inhibiting CD4+ T cell differentiation, decreasing CD4+ T cell proliferation, increasing apoptosis, and enhancing CCL2-induced migration in vitro, while reducing Th1 cell chemotaxis in vivo [1]. In children, genetic variation at the Npsr1 locus impacts the predisposition to recurrent abdominal pain (RAP), with certain Npsr1 SNPs associated with RAP [2]. In hemodialysis patients, the Ile-allele of Npsr1 Asn107Ile polymorphism was associated with an increased risk of anxiety [3].

In conclusion, Npsr1 plays a significant role in inflammation-related diseases like IBD and in pain-related conditions such as RAP. In addition, it is associated with anxiety in specific patient populations. The use of gene-knockdown models, including in mouse models for IBD, has been crucial in revealing these functions, providing insights into potential therapeutic strategies for related diseases.

References:

1. Peng, Yanan, Chen, Liping, Chen, Xiaojia, Ding, Feng, Wang, Xiaobing. 2024. NPSR1 promotes chronic colitis through regulating CD4+ T cell effector function in inflammatory bowel disease. In International immunopharmacology, 142, 113252. doi:10.1016/j.intimp.2024.113252. https://pubmed.ncbi.nlm.nih.gov/39332092/

2. Henström, M, Zucchelli, M, Söderhäll, C, Olén, O, D'Amato, M. 2014. NPSR1 polymorphisms influence recurrent abdominal pain in children: a population-based study. In Neurogastroenterology and motility, 26, 1417-25. doi:10.1111/nmo.12401. https://pubmed.ncbi.nlm.nih.gov/25091462/

3. Alshogran, Osama Y, Al-Eitan, Laith N, Altawalbeh, Shoroq M, Aman, Hatem A, Alhawari, Hussein H. 2019. Investigating the Contribution of NPSR1, IL-6 and BDNF Polymorphisms to Depressive and Anxiety Symptoms in Hemodialysis Patients. In Progress in neuro-psychopharmacology & biological psychiatry, 94, 109657. doi:10.1016/j.pnpbp.2019.109657. https://pubmed.ncbi.nlm.nih.gov/31132388/

4. Fang, Chao, Zhang, Jiannan, Wan, Yiping, Li, Juan, Wang, Yajun. 2021. Neuropeptide S (NPS) and its receptor (NPSR1) in chickens: cloning, tissue expression, and functional analysis. In Poultry science, 100, 101445. doi:10.1016/j.psj.2021.101445. https://pubmed.ncbi.nlm.nih.gov/34634709/