Expression of matrix metalloproteinase-3 in mouse endometrial stromal cells during early pregnancy: regulation by interleukin-1alpha and tenascin-C.
During the peri-implantation period, the endometrium undergoes tissue remodeling and cellular rearrangement. To clarify the involvement of matrix metalloproteinases (MMPs) in endometrial remodeling, we isolated total RNAs from the endometrium of non-pregnant and pregnant mice on days 3 to 5 and evaluated mRNA expression of MMP-2, -3, -9, -11 and -13 using reverse transcription-polymerase chain reaction (PCR). Prompt increases in MMP-3 and -13 mRNA were found on day 4 of pregnancy. Quantitative real-time PCR showed that expression of MMP-3 and -13 increased significantly on day 4, up to 8.4 +/- 2.7 times and 3.4 +/- 1.5 times, respectively, the level in non-pregnant endometrium (p < 0.05). On day 4, immunohistochemistry demonstrated MMP-3-positive endometrial stromal cells. At the same time, tenascin-C (TN-C) mRNA increased 11.1 +/- 4.0 times from the level in non-pregnant endometrium (p < 0.004). To clarify regulation of MMP-3 expression, we examined the effects of interleukin-1alpha (IL-1alpha) and TN-C on MMP-3 mRNA in cultured mouse endometrial stromal cells. Both substances resulted in a dose-dependent increase in MMP-3 mRNA (6.1 +/- 1.8-fold at 1 ng/ml of IL-1alpha and 3.9 +/- 1.8-fold at 10 mug/ml of TN-C). This study shows that MMP-3 expression is upregulated in endometrial stromal cells of the peri-implantation period and may be controlled by IL-1alpha and TN-C.
Nishiura
Rika
R
Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Noda
Naomi
N
Minoura
Hiroyuki
H
Toyoda
Nagayasu
N
Imanaka-Yoshida
Kyoko
K
Sakakura
Teruyo
T
Yoshida
Toshimichi
T
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D010064:Embryo Implantation / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D019063:Tenascin / Q000494:pharmacology*; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019063:Tenascin; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D019278:Matrix Metalloproteinase 3