title: A Common Variant of PROK1 (V67I) Acts as a Genetic Modifier in Early Human Pregnancy through Down-Regulation of Gene Expression.
abstract: PROK1-V67I has been shown to play a role as a modifier gene in the PROK1-PROKR system of human early pregnancy. To explore the related modifier mechanism of PROK1-V67I, we carried out a comparison study at the gene expression level and the cell function alternation of V67I, and its wild-type (WT), in transiently-transfected cells. We, respectively, performed quantitative RT-PCR and ELISA assays to evaluate the protein and/or transcript level of V67I and WT in HTR-8/SV neo, JAR, Ishikawa, and HEK293 cells. Transiently V67I- or WT-transfected HTR-8/SV neo and HEK293 cells were used to investigate cell function alternations. The transcript and protein expressions were down-regulated in all cell lines, ranging from 20% to 70%, compared with WT. There were no significant differences in the ligand activities of V67I and WT with regard to cell proliferation, cell invasion, calcium influx, and tubal formation. Both PROK1 alleles promoted cell invasion and intracellular calcium mobilization, whereas they had no significant effects on cell proliferation and tubal formation. In conclusion, the biological effects of PROK1-V67I on cell functions are similar to those of WT, and the common variant of V67I may act as a modifier in the PROK1-PROKR system through down-regulation of PROK1 expression. This study may provide a general mechanism that the common variant of V67I, modifying the disease severity of PROK1-related pathophysiologies.
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. sumeitsz@mail.ncku.edu.tw.
authors.forename: Mei-Tsz
authors.initials: MT
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. yyuangtw@mail.ncku.edu.tw.
authors.forename: Jyun-Yuan
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. cuteyling@gmail.com.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Department of Economics, National Cheng Kung University, Tainan 704, Taiwan. yichi@mail.ncku.edu.tw.
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. paolink@mail.ncku.edu.tw.
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005768:Gastrointestinal Hormones / Q000235:genetics* / Q000378:metabolism*; D060045:Genes, Modifier; D057809:HEK293 Cells; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005768:Gastrointestinal Hormones; C467610:PROK1 protein, human; D043562:Receptors, G-Protein-Coupled; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D002118:Calcium
keywords: EG-VEGF); Prokineticin 1 (PROK1; calcium influx; cell invasion; modifier gene; recurrent miscarriage
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