Cardiac regeneration: epicardial mediated repair

The hearts of lower vertebrates such as fish and salamanders display scarless regeneration following injury, although this feature is lost in adult mammals. The remarkable capacity of the neonatal mammalian heart to regenerate suggests that the underlying machinery required for the regenerative process is evolutionarily retained. Recent studies highlight the epicardial covering of the heart as an important source of the signalling factors required for the repair process. The developing epicardium is also a major source of cardiac fibroblasts, smooth muscle, endothelial cells and stem cells. Here, we examine animal models that are capable of scarless regeneration, the role of the epicardium as a source of cells, signalling mechanisms implicated in the regenerative process and how these mechanisms influence cardiomyocyte proliferation. We also discuss recent advances in cardiac stem cell research and potential therapeutic targets arising from these studies.     

Participation of the coelomic epithelium of the body wall in muscle regeneration in <Emphasis Type="Italic">Apostichopus japonicus</Emphasis> (Holothuroidea: Aspidochirota)

The cellular sources of regeneration of longitudinal muscles were studied in the holothurian Apostichopus japonicus. An autoradiographic method tracing the distribution of cells labeled with tritiated thymidine (³HT) revealed that the majority of ³HT-cells, which were initially localized in the coelomic epithelium of muscles and the body wall at the beginning of active morphogenesis, were then found in the structure of new muscular bundles during subsequent terms of restoration. Thus, the coelomic epithelium of the body wall participated in the regeneration of muscle tissue concurrently with the coelomic epithelium of muscle, contributing to the recruitment of a pool of myogenic cells.     

Ultrastructure of tentacles in the sipunculid worm <Emphasis Type="Italic">Thysanocardia nigra</Emphasis> Ikeda, 1904 (Sipuncula)

The ultrastructure of the tentacles was studied in the sipunculid worm Thysanocardia nigra. Flexible digitate tentacles are arranged into the dorsal and ventral tentacular crowns at the anterior end of the introvert of Th. nigra. The tentacle bears oral, lateral, and aboral rows of cilia; on the oral side, there is a longitudinal groove. Each tentacle contains two oral tentacular canals and an aboral tentacular canal. The oral side of the tentacle is covered by a simple columnar epithelium, which contains large glandular cells that secrete their products onto the apical surface of the epithelium. The lateral and aboral epithelia are composed of cuboidal and flattened cells. The tentacular canals are lined with a flattened coelomic epithelium that consists of podocytes with their processes and multiciliated cells. The tentacular canals are continuous with the radial coelomic canals of the head and constitute the terminal parts of the tentacular coelom, which shows a highly complex morphology. Five tentacular nerves and circular and longitudinal muscle bands lie in the connective tissue of the tentacle wall. Similarities and differences in the tentacle morphology between Th. nigra and other sipunculan species are discussed.Original Russian Text Copyright © 2005 by Biologiya Morya, Maiorova, Adrianov.     

Cellular retinoic acid-binding protein and its relationship to the biological activity of four synthetic retinoids in hamster tracheal organ culture

Summary The mechanism of action of retinoid in reversing keratinization in hamster trachea is yet unknown. The purpose of this study was to determine if cellular retinoic acid binding protein (CRABP) is present in tracheal epithelium following incubation in serum-free, vitamin A-deficient culture medium for 10 days, and if the effectiveness of a retinoid in reversing keratinization in organ culture is correlated with its ability to compete for CRABP sites. The cytosol prepared from tracheal cultures contained CRABP at a concentration of 2.61 pmoles per mg protein. Of the four retinoids with carboxyl end group selected for the study, two of the biological active retinoids competed for the CRABP sites. However, no correlation was observed between the biological activity of the inactive retinoids and their ability to associate with the CRABP sites. These results indicate that even though the action of retinoid may be mediated by retinoid binding protein, it cannot be used as a sole predicator of retinoid response in hamster trachea. This investigation was supported by Contract N01-CP-31012 and U. S. P. H. Grants CA30512 and CA32428, which were awarded by the Division of Cancer Etiology, National Cancer Institute, DHHS. Editor's Statement Tracheal organ cultures provide a useful model for the study of epithelial differentiation and carcinogenesis. Much attention has been given to the action of retinoids in this process. Mehta et al. demonstrate a lack of correlation between biological activity and specific cytosolic binding of members of this class of compounds, pointing out the need for a more complete biochemical understanding of the mechanism of action and active forms of retinoids in this and other systems in vivo and in vitro. David W. Barnes     

细胞内视黄酸信号传递系统

视黄酸对基因表达的调控与肿瘤细胞的分化、胚胎的发育以及疾病的发生关系密切．视黄酸的基因调控作用是通过视黄酸信号传递系统实现的．视黄酸信号传递系统包括视黄酸、细胞液视黄醇（酸）结合蛋白、视黄酸细胞核受体及视黄酸反应元件等．视黄酸信号传递系统自成一体系,在这一系列调控的级联反应中存在着多级反馈调控环节,而且该系统还与视黄酸配体以外的信号系统相联系．     

视黄类受体与视黄酸致畸作用关系

视黄酸（维甲酸）可引起包括人在内的多种动物胚胎畸形,其生物活性是由一系列视黄酸受体及其配体介导的。其中视黄类受体RAR起主要作用,RAR的配体为强致畸物,相对致畸活性由强至弱依次为配体α、配体β和配体γ。视黄酸受体RXR的配体无致畸活性,但是可加强RAR激动剂的某些致畸郊应。视黄酸受体还可通过其它基因的表达而影响胚胎发育。对视黄类受体基因突变和不同视黄类受体及其配体与致畸作用的关系,以及此类受体对其它基因表达的调节作简要综述。Abstract: Retinoic acid can induce teratogenesis of the fetus of many animals including human, and its biological activities are induced by a serious of different retinoic acid accepters and their ligands. The retinoic acid acceptor RAR plays key roles in the teratogenesis, and the legands of RAR are strong teratogens. The intensity sequence of the relative teratogenesis is ligandα、ligandβ and ligandγ. The ligands of the retinoic acid acceptor RXR cannot induce teratogenesis, but they can enhance the teratogenesis of the RAR stimulus. The retinoic acid acceptors can also affect the development of the fetus by adjusting the expression of the other genes. The relations between the gene mutation of the retinoic acid acceptor, various retinoic acid acceptors and their ligands and teratogenesis of retinoic acid are summarized in this article. In addition, the regulations of the retinoic acid acceptors to the other genes are also discussed.     

Myofibrillar adaptations during cardiac hypertrophy

The main purpose of this study was to determine the transmural adaptive changes that occur in cell size, myofibrils, and myosin isoforms from the endocardium (ENDO) to the epicardium (EPI) of the left ventricle (LV) of the rat heart during compensatory hypertrophy. Hypertrophy was induced by supra-renal aortic constriction for periods of 2, 7, 15 and 30 days. Percent left ventricular hypertrophy averaged 63±9.7% at 30 days following constriction. A significant (p <0.05) transmural gradient in the V₃ myosin isoform (9±0.7% ENDO vs. 5±1.8% EPI) was initially observed at 7 days and was still evident by 30 days (25±3.6% ENDO vs 15±2.0% EPI). Cell cross-sectional area was also greater (p <0.05) in the ENDO than in the EPI at 7,15 and 30 days. MF diameter was determined only at 30 days and was found to be similar to control values in both the hypertrophied ENDO (sham 1.24±0.05 vs hyp 1.18±0.09 m) and EPI (sham 1.17±0.08 vs hyp 1.06±0.08 m). The combined effects of cardiac myocyte hypertrophy with no change in MF diameter resulted in a calculated increase of approximately 70% in the number of myofibrils per myocyte both in the ENDO and EPI. It was concluded that the adaptive strategy of the left ventricular free wall to pressure overload was to initially increase myocyte cross-sectional area and then switch myosin expression from V₁ to V₃, both of which proceeds transmurally from the sub-endocardium towards the sub-epicardium. Along with these transmural adaptations, myofibrils increased in number while maintaining myofibrillar diameter with the apparent intent of conserving diffusion distance for calcium from the sarcoplasmic reticulum to the innermost contractile filaments of the myofibrils.     

心外膜的起源与发育

长期以来,心外膜被认为是起源于胚胎发育早期心管的最外层原始心肌.然而近来的研究表明,心外膜并非起源于原始心肌,而是起源于一个叫做前心外膜浆膜的原始心外原基.进一步研究表明,前心外膜浆膜和新形成的心外膜为心外膜下、心肌之中的相关组织以及冠状血管提供了几乎所有的细胞原基.最近的信息甚至表明心外膜及其它前心外膜起源的细胞在胚胎心肌和心传导系统的分化中起着重要的调节作用.     

Altered retinoic acid signalling underpins dentition evolution

Small variations in signalling pathways have been linked to phenotypic diversity and speciation. In vertebrates, teeth represent a reservoir of adaptive morphological structures that are prone to evolutionary change. Cyprinid fish display an impressive diversity in tooth number, but the signals that generate such diversity are unknown. Here, we show that retinoic acid (RA) availability influences tooth number size in Cyprinids. Heterozygous adult zebrafish heterozygous for the cyp26b1 mutant that encodes an enzyme able to degrade RA possess an extra tooth in the ventral row. Expression analysis of pharyngeal mesenchyme markers such as dlx2a and lhx6 shows lateral, anterior and dorsal expansion of these markers in RA-treated embryos, whereas the expression of the dental epithelium markers dlx2b and dlx3b is unchanged. Our analysis suggests that changes in RA signalling play an important role in the diversification of teeth in Cyprinids. Our work illustrates that through subtle changes in the expression of rate-limiting enzymes, the RA pathway is an active player of tooth evolution in fish.