3-Phosphoglycerate dehydrogenase expression is regulated by HOXA10 in murine endometrium and human endometrial cells.
3-Phosphoglycerate dehydrogenase (PHGDH, 3-PGDH) is an enzyme necessary for de novo l-serine biosynthesis. HOXA10 expression is required for endometrial receptivity; however, few target genes of HOXA10 regulation are known. Using a microarray we identified Phgdh as a target of HOXA10 regulation in murine endometrium and confirmed this regulatory relationship in human endometrial cells. PHGDH was downregulated 2.0-fold by HOXA10 and upregulated 4.4-fold by HOXA10 antisense in vivo. In human endometrial cells, real-time PCR results show that pcDNA3.1/HOXA10 transfection decreased PHGDH mRNA expression to 40% of pretreatment level (P<0.05), while PHGDH mRNA expression was increased 2.1-fold (P<0.05) by HOXA10 siRNA. Western blot results confirmed the regulatory relationship in both primary human endometrial stromal and epithelial cells, as well as in human endometrial stromal cells and Ishikawa cells. In human cycling endometrial tissue, immunohistochemical results showed that PHGDH expression is relatively high in the proliferative phase in glandular cells and lower in the secretory phase. Here we report novel expression and regulation of PHGDH in murine and human endometrium. PHGDH is expressed in both endometrial epithelial and stromal cells. HOXA10 represses endometrial PHGDH expression. PHGDH is necessary for serine biosynthesis, which serves as a substrate for protein synthesis. One mechanism by which HOXA10 regulates cellular differentiation may involve limiting protein synthesis in the secretary phase.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, PO Box 208063, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Hongling
H
Du
Danielle
D
Vitiello
Jennifer L
JL
Sarno
Hugh S
HS
Taylor
D000328:Adult; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014162:Transfection / Q000379:methods
D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C069634:HOXA10 protein, human; C092119:Hoxa10 protein, mouse; D050543:Phosphoglycerate Dehydrogenase