Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo

Abstract

Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo. Here, we report a detailed expression analysis of Mt4-mmp during mouse embryonic development by using a LacZ reporter transgenic mouse line. We showed that Mt4-mmp is detected from early stages of development to postnatal stages following a dynamic and restricted pattern of expression. Mt4-mmp was first detected at E8.5 limited to the intersomitic vascularization, the endocardial endothelium and the dorsal aorta. Mt4-mmpLacZ/+ cells were also observed in the neural crest cells, somites, floor plate and notochord at early stages. From E10.5, expression localized in the limb buds and persists during limb development. A strong expression in the brain begins at E12.5 and continues to postnatal stages. Specifically, staining was observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, septum, dorsal thalamus and the spinal cord. In addition, LacZ-positive cells were also detected during eye development, initially at the hyaloid artery and later on located in the lens and the neural retina. Mt4-mmp expression was confirmed by quantitative RT-PCR and western blot analysis in some embryonic tissues. Our data point to distinct functions for this metalloproteinase during embryonic development, particularly during brain formation, angiogenesis and limb development.

SP1‐mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR‐214‐3p/MMP2 axis

“…Interaction analysis by RT‐PCR and Western blot illustrated that MMP2 protein level was negatively correlated with miR‐214‐3p, which was positively correlated with PVT1. The modulators matrix metalloproteinases (MMPs) family plays critical roles in the TGFβ2‐mediated matrix contraction . Besides, MMP2 is closely correlated with the proliferation of lens epithelial cells.…”

“…The modulators matrix metalloproteinases (MMPs) family plays critical roles in the TGFβ2-mediated matrix contraction. [26][27][28] Besides, MMP2 is closely correlated with the proliferation of lens epithelial cells. Therefore, lncRNA PVT1 could regulate the HLE B-3 cell biological activity via modulating the MMP2.…”

The Role of Matrix Metalloproteinases in the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

“…MMP-17 is a relatively newly discovered membrane-type MMP that is glycosylphosphatidylinositol- (GPI-) anchored, but little information is available in regard to its physiological roles [78]. No involvement of MMP-17 in the EMT of HCC was found in the literature, but it was implicated in breast cancer progression, apparently by facilitating in vivo and in vitro breast cancer cell proliferation through outside-in EGFR signaling, but without acting as a protease [79].…”

Neural crest delamination and migration: Looking forward to the next 150 years

“…Nevertheless, MMP17 is expressed in several tissues including intersomitic vascularization endocardial endothelium, dorsal aorta, NC cells, somites, floor plate of the neural tube, notochord, and limbs. So far, no function has been analyzed in NC cells (Blanco et al, ).…”