Alternative titles; symbols
HGNC Approved Gene Symbol: PTGFR
Cytogenetic location: 1p31.1 Genomic coordinates (GRCh38): 1:78,490,974-78,540,701 (from NCBI)
Prostaglandin F(2-alpha) is involved in a number of physiologic processes. It serves as a potent luteolytic agent in many species, has been implicated as a modulator of intraocular pressure, and may be important in smooth muscle contraction in the uterus and elsewhere. Its effects on cells are mediated through specific interaction with prostaglandin receptors. Abramovitz et al. (1994) cloned a cDNA encoding the human prostanoid FP receptor from a uterus cDNA library. The 359-amino acid protein has 7 putative transmembrane domains characteristic of the G protein-coupled receptors. As expected, expression studies of the cDNA in Xenopus oocytes and COS cells showed strongest binding to PGF(2-alpha).
Betz et al. (1999) showed that the human PTGFR gene consists of 3 exons spanning approximately 10 kb of genomic DNA. The first exon is noncoding.
Duncan et al. (1995) mapped the PTGFR gene to 1p31.1 by in situ hybridization. Using a panel of interspecific backcross mice, Ishikawa et al. (1996) mapped the Ptgfr gene to distal mouse chromosome 3.
In a bleomycin-induced mouse model of pulmonary fibrosis (see 178500), Oga et al. (2009) demonstrated that loss of PTGFR selectively attenuated pulmonary fibrosis while maintaining levels of alveolar inflammation and TGFB (190180) stimulation similar to those of wildtype mice, and that PTGFR deficiency and inhibition of TGFB signaling additively decreased fibrosis. PGF(2-alpha) was found to be abundant in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis; in addition, PGF(2-alpha) stimulated proliferation and collagen production of lung fibroblasts via PTGFR independently of TGFB. Oga et al. (2009) concluded that PTGFR signaling facilitates pulmonary fibrosis independently of TGFB.
Latanoprost, a prostaglandin F(2-alpha) analog, is widely used to lower intraocular pressure in patients with glaucoma, although in some cases the response is unexpectedly weak. To study the basis of the variation in response to latanoprost, Sakurai et al. (2007) studied the relationship of response to polymorphisms of the PTGFR gene. They found that 2 single-nucleotide polymorphisms (SNPs) in the promoter and intron 1 regions of the FP receptor gene correlated with the response to short-term latanoprost treatment in normal volunteers. Sakurai et al. (2007) concluded that the genotype of these SNPs may be an important determinant of variability in response to latanoprost.
Sugimoto et al. (1997) showed that knockout mice lacking the receptor for prostaglandin F(2-alpha) are unable to deliver normal fetuses at term due to a lack of response to oxytocin. The mice also failed to show the decline in serum progesterone expected to precede parturition. However, if the mice had their ovaries removed at day 19 of pregnancy, normal delivery occurred. The authors concluded that parturition is initiated when prostaglandin F(2-alpha) interacts with its receptor in ovarian luteal cells to induce luteolysis. Sugimoto et al. (1997) also suggested that this mechanism may explain why aspirin-like drugs delay parturition.
Abramovitz, M., Boie, Y., Nguyen, T., Rushmore, T. H., Bayne, M. A., Metters, K. M., Slipetz, D. M., Grygorczyk, R. Cloning and expression of a cDNA for the human prostanoid FP receptor. J. Biol. Chem. 269: 2632-2636, 1994. [PubMed: 8300593]
Betz, R., Lagercrantz, J., Kedra, D., Dumanski, J. P., Nordenskjold, A. Genomic structure, 5-prime flanking sequences, and precise localization in 1p31.1 of the human prostaglandin F receptor gene. Biochem. Biophys. Res. Commun. 254: 413-416, 1999. [PubMed: 9918852] [Full Text: https://doi.org/10.1006/bbrc.1998.9827]
Duncan, A. M. V., Anderson, L. L., Funk, C. D., Abramovitz, M., Adam, M. Chromosomal localization of the human prostanoid receptor gene family. Genomics 25: 740-742, 1995. [PubMed: 7759114] [Full Text: https://doi.org/10.1016/0888-7543(95)80022-e]
Ishikawa, T., Tamai, Y., Rochelle, J. M., Hirata, M., Namba, T., Sugimoto, Y., Ichikawa, A., Narumiya, S., Taketo, M. M., Seldin, M. F. Mapping of the genes encoding mouse prostaglandin D, E, and F and prostacyclin receptors. Genomics 32: 285-288, 1996. [PubMed: 8833158] [Full Text: https://doi.org/10.1006/geno.1996.0118]
Oga, T., Matsuoka, T., Yao, C., Nonomura, K., Kitaoka, S., Sakata, D., Kita, Y., Tanizawa, K., Taguchi, Y., Chin, K., Mishima, M., Shimizu, T., Narumiya, S. Prostaglandin F2-alpha receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-beta. Nature Med. 15: 1426-1430, 2009. [PubMed: 19966781] [Full Text: https://doi.org/10.1038/nm.2066]
Sakurai, M., Higashide, T., Takahashi, M., Sugiyama, K. Association between genetic polymorphisms of the prostaglandin F(2-alpha) receptor gene and response to latanoprost. Ophthalmology 114: 1039-1045, 2007. Note: Erratum: Ophthalmology 114: 2012 only, 2007. [PubMed: 17467803] [Full Text: https://doi.org/10.1016/j.ophtha.2007.03.025]
Sugimoto, Y., Yamasaki, A., Segi, E., Tsuboi, K., Aze, Y., Nishimura, T., Oida, H., Yoshida, N., Tanaka, T., Katsuyama, M., Hasumoto, K., Murata, T., Hirata, M., Ushikubi, F., Negishi, M., Ichikawa, A., Narumiya, S. Failure of parturition in mice lacking the prostaglandin F receptor. Science 277: 681-683, 1997. [PubMed: 9235889] [Full Text: https://doi.org/10.1126/science.277.5326.681]