Tissue transglutaminase at embryo-maternal interface.
BACKGROUND
Tissue transglutaminase (tTG) has a high affinity for fibronectin (FN) and is a coreceptor of both beta1 and beta3 integrin subunits. Considering the notion that FN and integrins have critical roles during the implantation process, this study was undertaken to elucidate the expression pattern and the potential physiological function of tTG at the embryo-maternal interface.


METHODS
The primary cultures of human placentas from 15 legal elective abortions at the first trimester of normal pregnancies and endometrial biopsies of 12 female patients in the midluteal phase as well as normal trophoblastic cell lines (CRL) were employed to address these issues using several approaches, such as scanning and transmission electron microscopies, immunostaining for light and electron microscopies, western blotting, and function assays using GRGDSP hexapeptide and an antibody against tTG.


RESULTS
The results demonstrated tTG expression on uterine pinopodes and lamellipodia of extravillous trophoblasts. The colocalization of tTG with beta1 and beta3 integrins and its interaction with alpha(v)beta3 integrin and integrin-associated proteins at focal adhesions of the extravillous trophoblasts were illustrated in the results of immunofluorescence, immunoblot, and coimmunoprecipitation studies. Furthermore, function assays revealed that tTG mediated the adhesion and spread of the placental cells on intact FN-coated and 42- and 110-kDa FN fragment-coated wells.


CONCLUSIONS
In conclusion, our findings demonstrated for the first time that tTG actively participates in adhesion events at the embryo-maternal interface through its interaction with FN, at least in part, by activating integrin-signaling pathways.
Kabir-Salmani
Maryam
M
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan. kabirs_m@yahoo.com
Shiokawa
Shigetatsu
S
Akimoto
Yoshihiro
Y
Sakai
Keiji
K
Sakai
Ken
K
Iwashita
Mitsutoshi
M
D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides; D011247:Pregnancy; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction / Q000502:physiology; D011503:Transglutaminases / Q000378:metabolism*; D014327:Trophoblasts / Q000201:enzymology* / Q000648:ultrastructure*
D005353:Fibronectins; D019012:Integrin beta1; D039661:Integrin beta3; D009842:Oligopeptides; C080035:thymohexin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins