Expression of collagenase and IL‐1α in developing rat hearts

Abstract

During development, extracellular matrix (ECM) molecules are thought to play a major role in regulating the formation of the heart. The change in the heart from a simple tube to a complex, four-chambered organ requires the modification of both the cellular components as well as the surrounding ECM. Matrix metalloproteinases (MMP), which include collagenases, are enzymes present in the ECM that have the potential to modify the existing ECM during the development of the heart. Using both monoclonal and polyclonal antisera against collagenase, specific temporal and spatial patterns have been documented during critial periods of heart development. The cytokine interleukin la (IL-la), a potent inducer of the MMP expression, was also shown to have a similar staining pattern in the developing heart.The monoclonal anti-rat collagenase (Mab) intensely stained the surfaces of the myocytes in the trabeculae and the ventricular and atrial walls of the 11.5 or 12.5 embryonic day (ED) rat hearts. In contrast, the polyclonal anti-human collagenase (Pab) stained not only the cardiomyocytes but also the hypertrophic endocardial cells. Pab appeared to stain the leading edge of the mesenchyma1 cells that migrate into the cardiac jelly of the 11.5 or 12.5 ED hearts. Immunohistochemical staining showed IL-la on the endocardial endothelium and the surface of cardiomyocytes near the cardiac jelly just before or coincident with the appearance of migrating cells.IL-la was detected on the endocardial endothelium, cardiomyocytes in the trabeculae, and the ventricular and atrial walls, as well as in the myocardial basement membrane of the truncal or atrioventricular region. However, no staining could be detected on the migrating cells in the cardiac cushions. These results indicate the presence of collagenase and IL-la on the surface of cardiomyocytes and mesenchymal cells at times when the heart is undergoing acute remodeling during septation and trabeculation. These data suggest a role for collagenase/cytokine interaction in tissue remodeling during critical stages of cardiac em-

Cardiac morphogenesis: Matrix metalloproteinase coordination of cellular mechanisms underlying heart tube formation and directionality of looping

“…Because the dorsal mesocardium region first elongates, then constricts during heart development, and lastly breaks down to allow for the completion of looping, it was hypothesized that many of these remodeling processes may be mediated by temporally and spatially restricted MMP activity. Expression patterns of MMP-2 in the heart have been published previously (Cai et al, 2000;Ratajska and Cleutjens, 2002;Nakagawa et al, 1992), but these studies did not address the dorsal mesocardium. Knockout mice have been made for many of the metalloproteinases, but these models have not given unequivocal results, because the specific MMP knocked out can be compensated for by other MMPs.…”

“…MMP-2 mRNA and MMP-2 protein localization within the embryonic heart and neural crest regions were shown previously immunohistochemically; MMP activity was demonstrated by zymography (Nakagawa et al, 1992;Alexander et al, 1997;Cai et al, 2000;Ratajska and Cleutjens, 2002). Our analysis was to focus on the spatiotemporal localization in the developing dorsal mesocardial and foregut areas that previously had not been analyzed.…”

Expression of Neuropsin mRNA in the Mouse Embryo and the Pregnant Uterus

“…to 14.5 d.p.c. Other proteases, collagen and urokinase, were reported to be expressed in trabeculae at a similar stage and were believed to regulate migration of the cells (McGuire and Orkin 1992;Nakagawa et al 1992). That the neuropsin gene expression also coincided with the active trabeculation might suggest a relationship between neuropsin and the migration of the cells forming the trabeculae.…”

Specialization at the Z line of cardiac myocytes

“…At the level of rin clusters also provide binding sites for several protein the sarcolemma, integrin receptors are concentrated at kinases which rapidly localize to focal adhesions in these sites [9] as are cadherins [53], annexin [54], growth response to integrin engagement [12]. These cytoplasmic factor receptors [55], and proteases [56]. These molecules signaling kinases include the protein tyrosine kinases have both an extracellular and intracellular domain indicat-ing their potential for both chemical and mechanical Major changes in the ECM occur when the physiology of communication.…”