MMP3 mediates E2-induced endometrial cell proliferation by releasing HB-EGF

抄録

[Introduction] Cyclic cell proliferation and endometrial remodeling during the estrous cycle is important to maintain normal endometrial function. It has been reported that endometrial cells are actively proliferating at the follicular stage in cattle. However, the control mechanism of this cell proliferation has not yet been clarified. Recently it has been reported the possibility that protease enzyme matrix metalloproteinase-3 (MMP3) can regulate the cell proliferation. In the present study, the function of MMP3 on the proliferation of endometrial cells was analyzed. [Materials and Methods] Bovine endometrial stroma (BES) and epithelial (BEE) cells were cultured in DMEM/F12 containing 10%FBS. Gene expression was analyzed by qPCR. Protein expression of MMP3 and HB-EGF were analyzed by casein zymography and western bottling, respectively. Cell proliferation was analyzed by automated cell counter. [Results] MMP3 highly expressed at follicle stage compared to luteal and implantation stage. E2 increased the gene expression and clearance of MMP3 in BES in vitro, but P4 and IFNα decreased the expression. E2 also increased the cell proliferation of BES, but the inhibitor of MMP3 and EGFR inhibited the proliferation induced by E2. Further, E2 increased the HB-EGF release in BES but MMP3 inhibitor suppressed this release. There was no direct effect of E2 on BEE cell proliferation. However, the condition medium of BES treated with E2 increased the BEE proliferation but was inhibited by EGFR inhibitor. It was shown that E2 induces MMP3 expression and promotes HB-EGF release from BES. These results suggested that MMP3 is involved in the proliferation mechanism of endometrial cells in the follicular stage.