Synthesis of sulfated glycosaminoglycans by the three cell types of the rabbit cornea in culture

Summary Rabbit corneal cells were cultivated for 21 days and then exposed to Na₂ ³⁵SO₄, a precursor of sulfated glycosaminoglycans (GAG). All 3 cell types of the cornea, the fibroblasts, the epithelial as well as the endothelial cells, synthesize GAG. The fractionation-patterns of the epithelial and endothelial GAG are almost identical and differ clearly from the one of fibrolastic GAG.Supported by SNSF, grant No. 3.534.71.     

Effect of Progesterone on the in vivo binding of estrogens by uterine cells

Summary Progesterone selectively inhibits estradiol upltake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.Acknowledgments. This work was supported by Grant No. 2015 From the Oficina Técnica de Desarrollo Cientifico y Creación Artística of the University of Chile.     

Epithelial cell processes in the development of the secondary palate in the mouse.

Ultrastructural studies of palatal shelves of Tuck A mice embryos aged 12.25-14.25 days show discontinuities of the epithelial basement membrane traversed by epithelial cell processes before the onset of midline degenerative changes.     

Apoptosis regulation in the mammary gland

Epithelial apoptosis has a key role in the development and function of the mammary gland. It is involved with the formation of ducts during puberty and is required to remove excess epithelial cells after lactation so that the gland can be prepared for future pregnancies. Deregulated apoptosis contributes to malignant progression in the genesis of breast cancer. Since epithelial cell apoptosis in the lactating mammary gland can be synchronised by forced weaning, it has been possible to undertake biochemical analysis of the pathways involved. Together with the targeted overexpression or deletion of candidate genes, these approaches have provided a unique insight into the complex mechanisms of apoptosis regulation in vivo. This review explores what is currently known about the triggers for apoptosis in the normal mammary gland, and how they link with the intrinsic apoptotic machinery.Received 23 September 2003; received after revision 13 February 2004; accepted 3 March 2004     

Soluble polysialylated NCAM: a novel player of the innate immune system in the lung

Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.     

Hypophysial hormones and a G1 block in the lens epithelium of the adult frog (Rana pipiens)

Summary Mechanical injury initself may be responsible for the transition of lens epithelial cells from the G₀ to the G₁ compartment of the cell cycle. This traverse which does not depend on DNA-dependent hypophysial hormones may be in part reversible.     

Electron microscopy of gastric mucosal innervation in rats

Summary Electron microscopy of the rat stomach has shown vagal innervation of gastric epithelial cells with contact points. Unmyelinated axons of diameter 0.06 and 0.20 m were demonstrated passing in the connective tissue between epithelial cells.     

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer’s disease

β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer’s disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer’s disease.     

Effect of progesterone on the in vivo binding of estrogens by uterine cells.

Progesterone selectively inhibits estradiol uptake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.     

Loss of CD24 expression promotes ductal branching in the murine mammary gland

CD24 is expressed on mammary stem cells and is used as a marker for their isolation, yet its function in the mammary gland still needs to be examined. Here we show that CD24 is expressed throughout the luminal epithelial cell layer, but only weakly in myoepithelial cells. During lactation, CD24 expression was suppressed within alveoli, but upregulated post-lactation, returning to a pre-pregnant spatial distribution. CD24-deficient mice exhibited an accelerated mammary gland ductal extension during puberty and an enhanced branching morphogenesis, resulting in increased furcation in the ductal structure. CD24−/− mammary epithelial cells were able to completely repopulate cleared mammary fat pads and to give rise to fully functional mammary glands. Together, these data suggest that while CD24 is expressed in mammary epithelium compartments thought to contain stem cells, CD24 is not a major regulator of mammary stem/progenitor cell function, but rather plays a role in governing branching morphogenesis.     

Synthesis of sulfated glycosaminoglycans by the three cell types of the rabbit cornea in culture.

Rabbit corneal cells were cultivated for 21 days and then exposed to Na235SO4, a precursor of sulfated glycosaminoglycans (GAG). All 3 cell types of the cornea, the fibroblasts, the epithelial as well as the endothelial cells, synthesize GAG. The fractionation-patterns of the epithelial and endotherlial GAG are almost identical and differ clearly from the one of fibroblastic GAG.     

Roles of the Skp2/p27 axis in the progression of chronic nephropathy

S-phase kinase-associated protein 2 (Skp2) is an F-box protein component of the Skp/Cullin/F-box-type E3 ubiquitin ligase that targets several cell cycle regulatory proteins for degradation through the ubiquitin-dependent pathway. Skp2-mediated degradation of p27, a cyclin-dependent kinase inhibitor, is involved in cell cycle regulation. Tubular epithelial cell proliferation is a characteristic feature of renal damage that is apparent in the early stages of nephropathy. The p27 level is associated with the progression of renal injury, and increased Skp2 expression in progressive nephropathy is implicated in decreases of p27 expression. In Skp2^?/? mice, renal damage caused by unilateral ureteral obstruction (UUO) was ameliorated by p27 accumulation, mainly in tubular epithelial cells. However, the amelioration of UUO-induced renal injury in Skp2^?/? mice was prevented by p27 deficiency in Skp2^?/?/p27^?/? mice. These results suggest that the Skp2-mediated reduction in p27 is a pathogenic activity that occurs during the progression of nephropathy. Here, we discuss the roles of the Skp2/p27 axis and/or related signaling pathways/components in the progression of chronic nephropathy.     

Scanning and transmission electron microscopic evidence of epithelial phagocytosis of spermatozoa in the terminal region of the vas deferens of the cat

Scanning and transmission electron microscopic observations have been made in the terminal region of the vas deferens of the cat, with emphasis on the occurrence of spermiophagy. The present study has revealed that epithelial cells as well as luminal macrophages are extensively and actively involved in phagocytosis of spermatozoa. The mechanism of the spermiophagy is discussed, in relation to a possible role of the epithelial cells, as one function of the vas deferens.     

Scanning and transmission electron microscopic evidence of epithelial phagocytosis of spermatozoa in the terminal region of the vas deferens of the cat

Summary Scanning and transmission electron microscopic observations have been made in the terminal region of the vas deferens of the cat, with emphasis on the occurrence of spermiophagy. The present study has revealed that epithelial cells as well as luminal macrophages are extensively and actively involved in phagocytosis of spermatozoa. The mechanism of the spermiophagy is discussed, in relation to a possible role of the epithelial cells, as one function of the vas deferens.     

Combined effects of testosterone and estradiol on the ventral lobe of the rat postate in organ culture]

After organ culture without hormone, the epithelial gland cells of Rat veantral prostate undergo atrophic changes, whereas the interstitial stroma components tend to increase. Estradiol (1-1,000 nM),added to the culture medium, is ineffective. On the contrary, testosterone (1-100 nM) maintains epithelial cells and prevents the increase of interstitial stroma. When estradiol (1-1,000 nM) is combined with a physiological concentration of testosterone (1-4 nM), the epithelial cells are well maintained, but the inhibitory action of testosterone on the stroma is counteracted so that the glandular epithelium and the interstitial stroma are both stimulated. However, when testosterone is used at supraphysiological (10-100 nM) concentrations, estradiol is completely ineffective and the structure of the prostate is identical to the one given by the androgen alone.     

E-cadherin plays an essential role in collective directional migration of large epithelial sheets

In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell-cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell-cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell-cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism--E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets.