Ciliated fibroblasts and smooth muscle cells in the rat uterus

Summary Ciliation in endometrial fibroblasts and myometrial muscle cells of the rat was examined by transmission electron microscopy. Quantification of the number of ciliated cells during the estrus cycle did not show any firm relationship between cilation and ovarian hormonal activity. In the case of most cilia, there is a spatial relationship between their basal centrioles and the Golgi complex, so that a Golgi-cilium complex is created. A possible role of ciliation in uterine fibroblasts and smooth muscle cells is discussed.     

Lipid mediators in epithelial cell-cell interactions

Epithelial cells which line mucosal surfaces (e.g. lung, intestine) play a central role in the coordination of the inflammatory response. In both the healthy and diseased mucosa, epithelia lie anatomically positioned in close proximity to a number of other cell types, including leukocytes, fibroblasts, smooth muscle cells and vascular endothelia. This complex architecture supports a unique microenvironment for biochemical cell-cell crosstalk. Our previous studies and work by others have elucidated lipid mediator signaling networks emanating from epithelial cell-cell interactive pathways, and have defined a number of targets for development of effective therapeutics. This short review will focus on recently defined pathways of lipid mediator function in the mucosa, particularly with regard to the role of the epithelium.     

Cardiovascular development: towards biomedical applicability

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium-derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular fibroblasts. Moreover, epicardium-derived cells are important regulators of formation of the compact myocardium, the coronary vasculature, and the Purkinje fiber network, thus being essential for proper cardiac development. The fibrous structures of the heart such as the fibrous heart skeleton and the semilunar and atrioventricular valves also depend on a contribution of these cells during development. We hypothesise that the essential properties of epicardium-derived cells can be recapitulated in adult diseased myocardium. These cells can therefore be considered as a novel source of adult stem cells useful in clinical cardiac regeneration therapy.     

Endothelial cells as antigen-presenting cells: role in human transplant rejection

The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’ positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection. Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998     

Cell cycle progression by the repression of primary cilia formation in proliferating cells

In most cell types, primary cilia protrude from the cell surface and act as major hubs for cell signaling, cell differentiation, and cell polarity. With the exception of some cells ciliated during cell proliferation, most cells begin to disassemble their primary cilia at cell cycle re-entry. Although the role of primary cilia disassembly on cell cycle progression is still under debate, recent data have emerged to support the idea that primary cilia exert influence on cell cycle progression. In this review, we emphasize a non-mitotic role of Aurora-A not only in the ciliary resorption at cell cycle re-entry but also in continuous suppression of cilia regeneration during cell proliferation. We also summarize recent new findings indicating that forced induction/suppression of primary cilia can affect cell cycle progression, in particular the transition from G0/G1 to S phase. In addition, we speculate how (de)ciliation affects cell cycle progression.     

Electrophoretic profiles of proteins and glycoproteins of chick embryo fibroblasts during development]

The variations of proteins and glycoproteins of Chick embryo fibroblasts are studied during development. This investigation is carried out using polyacrylamide disc gel electrophoresis in SDS. Two glycoproteins of high apparent molecular weight (250,000 and 200,000) undergo quantitative modification: they increase from the 8th to 12th day of development and then remain unchanged to the 16th day. They are cell surface components as suggested by fluorescamine labelling and trypsin sensitivity. The results are discussed in terms of relationship between tumor- and embryo cells.     

Intercellular communication in smooth muscle

The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling.Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle.Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling.     

The transverse-axial tubular system of cardiomyocytes

A characteristic histological feature of striated muscle cells is the presence of deep invaginations of the plasma membrane (sarcolemma), most commonly referred to as T-tubules or the transverse-axial tubular system (TATS). TATS mediates the rapid spread of the electrical signal (action potential) to the cell core triggering Ca²⁺ release from the sarcoplasmic reticulum, ultimately inducing myofilament contraction (excitation–contraction coupling). T-tubules, first described in vertebrate skeletal muscle cells, have also been recognized for a long time in mammalian cardiac ventricular myocytes, with a structure and a function that in recent years have been shown to be far more complex and pivotal for cardiac function than initially thought. Renewed interest in T-tubule function stems from the loss and disorganization of T-tubules found in a number of pathological conditions including human heart failure (HF) and dilated and hypertrophic cardiomyopathies, as well as in animal models of HF, chronic ischemia and atrial fibrillation. Disease-related remodeling of the TATS leads to asynchronous and inhomogeneous Ca²⁺-release, due to the presence of orphan ryanodine receptors that have lost their coupling with the dihydropyridine receptors and are either not activated or activated with a delay. Here, we review the physiology of the TATS, focusing first on the relationship between function and structure, and then describing T-tubular remodeling and its reversal in disease settings and following effective therapeutic approaches.     

Shivering during sleep: Relationship between muscle blood flow and fiber type composition

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.     

Fibroblast-to-myofibroblast transition in bronchial asthma

Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon.     

Shivering during sleep: relationship between muscle blood flow and fiber type composition.

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.     

Satellite cells in denervated muscles.

It is known that, in a denervated striated muscle, the satellite cells multiply by mitotic division. A liaison between these satellite cells and the Schwann cell in front of the post-synaptic membrane in denervated frog muscle has been observed. It is probable that such cell connections help in the subsistence of the Schwann cell in a denervated muscle.     

Relationship between size of muscle fibres and body dimensions in a number of teleosts.

In a survey of 17 species of teleosts, a direct relationship was found between the diameter of muscle fibres and estimated volume of the fish. The results also suggested an inverse relationship between muscle fibre diameter and 'streamlinedness' of the fish (as measured by length:height ratio).     

Satellite cells in denervated muscles

Summary It is known that, in a denervated striated muscle, the satellite cells multiply by mitotic division. A liaison between these satellite cells and the Schwann cell in front of the post-synaptic membrane in denervated frog muscle has been observed. It is probable that such cell connections help in the subsistence of the Schwann cell in a denervated muscle.     

An eicosanoid-centric view of atherothrombotic risk factors

Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world. Atherosclerosis followed by thrombosis (atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events. Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and proteins directly involved in these processes, traditional cardiovascular risk factors (hyperlipidemia, hypertension, smoking, diabetes mellitus, sex, and age) remain the most useful predictor of disease. Eicosanoids (20 carbon polyunsaturated fatty acid derivatives of arachidonic acid and other essential fatty acids) are emerging as important regulators of cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing eicosanoid signaling, have contributed to the lack of therapies directed at the eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between eicosanoids and cardiovascular risk factors.     

Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue

The dystrophin glycoprotein complex (DGC) is a multimeric protein assembly associated with either the X-linked cytoskeletal protein dystrophin or its autosomal homologue utrophin. In striated muscle cells, the DGC links the extracellular matrix to the actin cytoskeleton and mediates three major functions: structural stability of the plasma membrane, ion homeostasis, and transmembrane signaling. Mutations affecting the DGC underlie major forms of congenital muscle dystrophies. The DGC is prominent also in the central and peripheral nervous system and in tissues with a secretory function or which form barriers between functional compartments, such as the blood-brain barrier, choroid plexus, or kidney. A considerable molecular heterogeneity arises from cell-specific expression of its constituent proteins, notably short C-terminal isoforms of dystrophin. Experimentally, the generation of mice carrying targeted gene deletions affecting the DGC has clarified the interdependence of DGC proteins for assembly of the complex and revealed its importance for brain development and regulation of the ’milieu intérieur. Here, we focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discuss the role of dystrophin isoforms and utrophin for assembly of the complex in these tissues. Received 4 October 2005; received after revision 14 March 2006; accepted 5 April 2006     

<Emphasis Type="Italic">XPF</Emphasis> knockout via CRISPR/Cas9 reveals that ERCC1 is retained in the cytoplasm without its heterodimer partner XPF

The XPF/ERCC1 heterodimeric complex is essentially involved in nucleotide excision repair (NER), interstrand crosslink (ICL), and double-strand break repair. Defects in XPF lead to severe diseases like xeroderma pigmentosum (XP). Up until now, XP-F patient cells have been utilized for functional analyses. Due to the multiple roles of the XPF/ERCC1 complex, these patient cells retain at least one full-length allele and residual repair capabilities. Despite the essential function of the XPF/ERCC1 complex for the human organism, we successfully generated a viable immortalised human XPF knockout cell line with complete loss of XPF using the CRISPR/Cas9 technique in fetal lung fibroblasts (MRC5Vi cells). These cells showed a markedly increased sensitivity to UVC, cisplatin, and psoralen activated by UVA as well as reduced repair capabilities for NER and ICL repair as assessed by reporter gene assays. Using the newly generated knockout cells, we could show that human XPF is markedly involved in homologous recombination repair (HRR) but dispensable for non-homologous end-joining (NHEJ). Notably, ERCC1 was not detectable in the nucleus of the XPF knockout cells indicating the necessity of a functional XPF/ERCC1 heterodimer to allow ERCC1 to enter the nucleus. Overexpression of wild-type XPF could reverse this effect as well as the repair deficiencies.