Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells

Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E<sub>2</sub>), and progesterone (P<sub>4</sub>). Matrix metalloproteases (MMPs) and tissue inhi...

Full description

Bibliographic Details
Main Authors: Yoji Hisamatsu, Hiromi Murata, Hiroaki Tsubokura, Yoshiko Hashimoto, Masaaki Kitada, Susumu Tanaka, Hidetaka Okada
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/43/3/146
Description
Summary:Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E<sub>2</sub>), and progesterone (P<sub>4</sub>). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E<sub>2</sub> + medroxyprogesterone acetate (MPA), a potent P<sub>4</sub> receptor agonist, showed significant down-regulation of <i>MMP3</i>, <i>MMP10</i>, <i>MMP11</i>, <i>MMP12</i>, <i>MMP20</i>, and <i>MMP27</i> in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, <i>MMP15</i> and <i>MMP19</i> were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased <i>MMP15</i> expression in untreated human ESCs. These results collectively indicate the importance of <i>MMP15</i> and <i>MMP19</i> in ESC decidualization and highlight the role of HAND2 in repressing <i>MMP15</i> transcription, thereby regulating decidualization.
ISSN:1467-3037
1467-3045