Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing.
Lefty/Ebaf polypeptides, novel members of the TGF-beta superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form. Here, we show that decidual differentiation of endometrial stroma leads to increased lefty (approximately 3.1- to 3.6-fold in vivo and 5- to 8-fold in vitro) and processing of its precursor primarily to its long form. This event occurs on d 5 of pregnancy, and is paralleled by proprotein convertase (PC)5/6 up-regulation (approximately 6-fold increase for PC5A and 3-fold increase for PC5B) in decidualized uterine horn, independent of embryo implantation. Among the known convertases, only PC5/6A processes lefty to its long form. Taken together, the findings show that decidualized differentiation of stroma, which is a prerequisite for embryo implantation, leads to processing of lefty by PC5/6A.
Tang
Meiyi
M
Department of Obstetrics and Gynecology, Stony Brook University, New York 11794, USA.
Mikhailik
Anatoly
A
Pauli
Ilse
I
Giudice
Linda C
LC
Fazelabas
Asgerally T
AT
Tulac
Suzana
S
Carson
Daniel D
DD
Kaufman
David G
DG
Barbier
Claire
C
Creemers
John W M
JW
Tabibzadeh
Siamak
S
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003656:Decidua / Q000502:physiology*; D004717:Endometrium / Q000166:cytology*; D005260:Female; D055458:Left-Right Determination Factors; D051379:Mice; D011247:Pregnancy; D045702:Proprotein Convertase 5 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017154:Stromal Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D055458:Left-Right Determination Factors; C526162:Lefty2 protein, mouse; D016212:Transforming Growth Factor beta; D045702:Proprotein Convertase 5