Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation

Abstract

Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages. Integrin beta8 can functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK, and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for the attachment of blastocyst.

miR‑222 regulates brain injury and inflammation following intracerebral hemorrhage by targeting ITGB8

“…iTGB8 is an important member of the integrin family, members of which are mediators of the interactions between cells and the matrix (34). Previous studies have revealed that iTGB8 in perivascular astrocytes plays an important role in regulating brain vessel homeostasis through modulation of TGF-β activation and expression of TGF-β-responsive genes that promote vessel differentiation and stabilization (35).…”

Spatial Transcriptomic and miRNA Analyses Revealed Genes Involved in the Mesometrial-Biased Implantation in Pigs

“…Among the miRNAs differentially expressed between gestational days 12 and 15, miR-142-5p and miR-142-3p exhibited a negative expression pattern with ITGB 8, which could influence endometrial receptivity and regulate embryo attachment [41,42]. The 3′UTR region of ITGB 8 has a binding site for miR-142-3p, and this regulatory relationship has been reported in glioma [43].…”

Enhancement of Endometrial Receptivity by Cnidium officinale through Expressing LIF and Integrins

“…Another group has shown that various integrin subunits α 1, α 4, β 1, and β 5 were known to be expressed in endometrial epithelium during the implantation window [7]. Recently, Kumar et al [32] showed that integrin β 8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for blastocyst implantation. Previously, we also reported that LIF regulates endometrial receptivity via integrins α V β 3 and α V β 5 [18].…”