PTH2R,也称为PTH2受体,是一种G蛋白偶联受体,在哺乳动物中与PTH1R共同调节钙稳态。PTH2R与PTH1R的主要区别在于其内源性配体不同,PTH2R的内源性配体是TIP39(tuberoinfundibular peptide of 39 residues),而PTH1R的内源性配体是PTH(parathyroid hormone)[8]。PTH2R在哺乳动物中的表达主要集中在神经系统,包括大脑、脑干和脊髓,其在神经系统中的功能可能与调节内脏感觉信息的处理有关[6]。
PTH2R的表达和功能受到多种因素的调控。研究表明, Hedgehog(Hh)信号通路可以调节PTH2R的表达。在斑马鱼发育过程中,Hh信号通路可以调节PTH2的转录,进而影响PTH2R的表达[4]。此外,PTH2R的表达也受到基因变异的影响。例如,在老年女性中,PTH2R基因的SNP rs897083 A-allele与腰椎退行性变的发生相关[2]。
PTH2R在多种疾病中发挥重要作用。研究表明,PTH2R在卵巢癌中高表达,并且参与卵巢癌细胞的增殖、侵袭和转移。敲低PTH2R的表达可以抑制肿瘤细胞的增殖、侵袭和迁移[1]。此外,PTH2R的表达还受到环境因素的影响。例如,暴露于环境内分泌干扰物PFOA和PFOS可以降低PTH2R的表达,这可能与骨关节炎的发生有关[3]。另外,研究还发现,PTH2R基因的变异与中位颅缝早闭症的发生相关[5]。
PTH2R与TIP39的相互作用在神经系统中发挥重要作用。研究表明,TIP39和PTH2R在脑组织中的分布具有高度相关性,这表明TIP39可能通过作用于PTH2R来调节神经系统的功能[8]。此外,研究还发现,TIP39可以激活PTH2R,进而影响细胞内钙离子水平和cAMP信号通路[7]。
综上所述,PTH2R是一种重要的G蛋白偶联受体,在哺乳动物中与PTH1R共同调节钙稳态。PTH2R在神经系统中的功能可能与调节内脏感觉信息的处理有关,其表达和功能受到多种因素的调控,包括Hh信号通路、基因变异和环境因素。PTH2R在多种疾病中发挥重要作用,包括卵巢癌、骨关节炎和中位颅缝早闭症。PTH2R与TIP39的相互作用在神经系统中发挥重要作用,可能参与调节神经系统的功能。
参考文献:
1. Xiaowei, Wang, Tong, Lu, Yanjun, Qu, Lili, Fan. 2022. PTH2R is related to cell proliferation and migration in ovarian cancer: a multi-omics analysis of bioinformatics and experiments. In Cancer cell international, 22, 148. doi:10.1186/s12935-022-02566-2. https://pubmed.ncbi.nlm.nih.gov/35410353/
2. Åkesson, Kristina, Tenne, Max, Gerdhem, Paul, Luthman, Holger, McGuigan, Fiona E. 2013. Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine. In Journal of bone and mineral metabolism, 33, 9-15. doi:10.1007/s00774-013-0550-x. https://pubmed.ncbi.nlm.nih.gov/24378925/
3. Galloway, Tamara S, Fletcher, Tony, Thomas, Oliver J, Pilling, Luke C, Harries, Lorna W. 2014. PFOA and PFOS are associated with reduced expression of the parathyroid hormone 2 receptor (PTH2R) gene in women. In Chemosphere, 120, 555-62. doi:10.1016/j.chemosphere.2014.09.066. https://pubmed.ncbi.nlm.nih.gov/25462297/
4. Bhattacharya, Poulomi, Yan, Yi Lin, Postlethwait, John, Rubin, David A. 2011. Evolution of the vertebrate pth2 (tip39) gene family and the regulation of PTH type 2 receptor (pth2r) and its endogenous ligand pth2 by hedgehog signaling in zebrafish development. In The Journal of endocrinology, 211, 187-200. doi:10.1530/JOE-10-0439. https://pubmed.ncbi.nlm.nih.gov/21880859/
5. Kim, Juwon, Won, Hong-Hee, Kim, Yoonjung, Yu, Nae, Lee, Kyung-A. 2015. Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement. In Journal of medical genetics, 52, 706-9. doi:10.1136/jmedgenet-2015-103001. https://pubmed.ncbi.nlm.nih.gov/26044810/
6. Bagó, Attila G, Palkovits, Miklós, Usdin, Ted B, Seress, László, Dobolyi, Arpád. . Evidence for the expression of parathyroid hormone 2 receptor in the human brainstem. In Ideggyogyaszati szemle, 61, 123-6. doi:. https://pubmed.ncbi.nlm.nih.gov/18459453/
7. Bisello, Alessandro, Manen, Danielle, Pierroz, Dominique D, Rizzoli, René, Ferrari, Serge L. 2004. Agonist-specific regulation of parathyroid hormone (PTH) receptor type 2 activity: structural and functional analysis of PTH- and tuberoinfundibular peptide (TIP) 39-stimulated desensitization and internalization. In Molecular endocrinology (Baltimore, Md.), 18, 1486-98. doi:. https://pubmed.ncbi.nlm.nih.gov/14988434/
8. Faber, Catherine A, Dobolyi, Arpád, Sleeman, Mark, Usdin, Ted B. . Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain. In The Journal of comparative neurology, 502, 563-83. doi:. https://pubmed.ncbi.nlm.nih.gov/17394159/