Differential Regulation of Matrix Metalloproteinase-3 Gene Expression in Endometriotic Lesions Compared with Endometrium1

Abstract

In vivo levels of mRNA and the specificity of the extrauterine environment on matrix metalloproteinase (MMP)-3, MMP-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were evaluated in eutopic and ectopic endometrial tissue during the establishment of endometriosis in a rat model. Uteri and endometriotic implants were collected and frozen at 36 h, 2 wk, and 4 wk postsurgery to study in vivo mRNA levels. Intact uteri, uterine tissues implanted in the peritoneum or under the skin, and peritoneal adipose implants were collected at 2 wk, halved, and either frozen or cultured. Gene-specific reverse transcriptase-polymerase chain reaction was performed to detect and quantify MMP-2, MMP-3, and TIMP-1 mRNA levels. The peritoneal endometriotic implants progressed from avascularized implants, to vascularized red lesions, to well-established encapsulated cysts. In vivo, MMP-3 mRNA was detectable at all times in ectopic tissues but not in eutopic uterine tissues, whereas MMP-2 and TIMP-1 were ubiquitously expressed at all times in both tissues. In vitro, only MMP-3 mRNA levels were elevated in endometrial tissues collected from the intact uterine and from under the skin, at levels similar to in vivo endometriotic implant MMP-3. In conclusion, ectopic endometrial MMP-3 may participate in the process of invasion and tissue remodeling that is hypothesized to occur in the pathogenesis of endometriosis.

Proteasomes and Proteasome Activator 200 kDa (PA200) Accumulate on Chromatin in Response to Ionizing Radiation

“…For experiments 2 and 3, endometriosis was surgically induced in rats (Endo) as previously described by Vernon and Wilson [13] and routinely performed in our laboratory [19,21,33,34,37,38]. A unilateral ovariohysterectomy was performed, and sections of the removed uterus were autotransplanted into the arterial cascade of the small intestine.…”

“…Expression of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) is reportedly involved in the pathogenesis and pathophysiologies of endometriosis occurring in women and in animal models [17][18][19][20][21][22]. The MMPs are a family of enzymes that degrade the extracellular matrix, including basement membrane components [23].…”

Abnormal regulation of chemokine TECK and its receptor CCR9 in the endometriotic milieu is involved in pathogenesis of endometriosis by way of enhancing invasiveness of endometrial stromal cells

“…Alteration of MMP-9 and MMP-2 is an important factor in the development of endometriosis. [13][14][15][16][17][18] Recent studies have suggested that 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) and dioxin-like compounds are important in the development of endometriosis. TCDD is a prototype of the polyhalogenated aromatic hydrocarbons, a family of chemicals that have a common mechanism of action.…”

The Local Immune Mechanisms Involved in the Formation of Endometriotic Lesions

“…Up to now the prominent changes of MMPs production in animals with experimental endometriosis have been demonstrated. The level of MMP-3 and MMP-9 was significantly higher in endometriotic lesions in rats with experimental endometriosis than in matched eutopic endometrium (Machado et al, 2010;Cox et al, 2001). Suppression of MMP-2 and MMP-9 activity in mice led to the inhibition of endometriosis progression in animals with the decrease of endometriotic lesions weight (Chen et al, 2010).…”