scholarly journals Anti-fibrotic activity of an antimicrobial peptide in a Drosophila model

2021 ◽  
Author(s):  
Dilan Khalili ◽  
Christina Kalcher ◽  
Stefan Baumgartner ◽  
Ulrich Theopold
Keyword(s):  
Epithelial Cells ◽  
Basement Membrane ◽  
Antimicrobial Peptide ◽  
Cell Polarity ◽  
Active Form ◽  
Ectopic Expression ◽  
Secretory Activity ◽  
Ras Oncogene ◽  
Pathological Conditions ◽  
Drosophila Model

AbstractFibrotic lesions accompany several pathological conditions including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apico-basal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide Drosomycin (Drs), which also restores secretory activity of the SGs. In addition to ECM components, both Drs and F-actin localize to fibrotic lesions.

scholarly journals Anti-Fibrotic Activity of an Antimicrobial Peptide in a Drosophila Model

2021 ◽  
pp. 1-15
Author(s):  
Dilan Khalili ◽  
Christina Kalcher ◽  
Stefan Baumgartner ◽  
Ulrich Theopold
Keyword(s):  
Antimicrobial Peptide ◽  
Cell Polarity ◽  
Active Form ◽  
Ectopic Expression ◽  
Secretory Activity ◽  
Ras Oncogene ◽  
Apicobasal Polarity ◽  
Pathological Conditions ◽  
Extracellular Matrix Components ◽  
Matrix Components

Fibrotic lesions accompany several pathological conditions, including tumors. We show that expression of a dominant-active form of the Ras oncogene in <i>Drosophila</i> salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components, including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apicobasal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide drosomycin (Drs), which also restores the secretory activity of the SGs. In addition to extracellular matrix components, both Drs and F-actin localize to fibrotic lesions.

Surface Ultrastructure of Human Ectocervix in Certain Pathological Conditions

1985 ◽  
Vol 43 ◽  
pp. 570-571
Author(s):  
S. Mukherjee ◽  
T. Guha ◽  
B. Chakrabarti ◽  
P. Chakrabarti
Keyword(s):  
Epithelial Cells ◽  
Marked Reduction ◽  
Squamous Epithelium ◽  
Malignant Tumour ◽  
Surface Ultrastructure ◽  
Normal Tissues ◽  
Pathological Conditions ◽  
Hexagonal Shape ◽  
Columnar Cells ◽  
Scanning Electron

The cervix is an important organ in reproduction. Its malfunction is frequently a factor for infertility. Ectocervix region does not appear to have received much attention although many studies have been reported on the endocervix. We report here our SEM observations on ectocervix in certain pathological conditions compared to normal ectocervix.Ectocervix specimens from human females with specific pathological disorders were processed for Scanning Electron Microscopy by conventional method and they were examined in a Philips SEM.The normal ectocervix is lined by flat layer of squamous epithelial cells with microridges (Fig. 1). These cells are known to be formed from columnar cells through metaplastic transformation. The cells of carcinoma-bearing ectocervix show a disorganised appearance (Fig. 2). In non-malignant tumour surface some cuboidal and few columnar cells were seen (Fig. 3). A cyst appears like an overgrowth on the surface of the squamous epithelium (Fig. 4). In ulcerated ectocervix a marked reduction of epithelial cells are observed (Fig. 5); the cells are devoid of microridges and, the large polygonal cells, as observed in normal tissues, have somehow acquired comparatively small hexagonal shape

Electron microscope study of the secretory activity of epithelial cells in embryonic thymus

1990 ◽  
Vol 48 (3) ◽  
pp. 382-383
Author(s):  
H. Alasam
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
Electron Density ◽  
Secretory Activity ◽  
T Cell Differentiation ◽  
High Electron ◽  
Transmission Electron ◽  
Medullary Epithelial Cells ◽  
Thymic Factor

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).

Innovative approaches to the correction of chronotrope status of pregnant and lactating women

2016 ◽  
pp. 37-40
Author(s):  
S.I. Zhuk ◽  
◽  
K.K. Bondarenko ◽  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Active Form ◽  
Biologically Active ◽  
Lactating Women ◽  
Pathological Conditions ◽  
Prevention And Treatment ◽  
The Impact ◽  
High Bioavailability ◽  
Key Words Mthfr

Most recent studies show the impact of violations in the metabolism of folate and metin period in the pathogenesis of neural tube defects (NTD) of the fetus. Metafolin has a number of advantages, which primarily includes direct intake of substances in biologically active form and the optimum effect, even in the case when the patient homozygote and/or heterozygote genotype 677С T polymorphism in MTHFR. With the aim of prevention and treatment of various pathological conditions related to folate deficiency during pregnancy, it is advisable to apply vitamin-mineral complexes, containing metafolin - active form of folate with high bioavailability. Key words: MTHFR, metafolin, folic acid, pregnancy.

scholarly journals Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures

2001 ◽  
Vol 152 (6) ◽  
pp. 1183-1196 ◽  
Author(s):  
Atsushi Suzuki ◽  
Tomoyuki Yamanaka ◽  
Tomonori Hirose ◽  
Naoyuki Manabe ◽  
Keiko Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Protein Complex ◽  
Mdck Cells ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Surface Polarity ◽  
C Elegans ◽  
Evolutionarily Conserved

We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. elegans atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607–3614]. Together with the fact that aPKC and a mammalian PAR-3 homologue, aPKC-specific interacting protein (ASIP), colocalize at the tight junctions of polarized epithelial cells (Izumi, Y., H. Hirose, Y. Tamai, S.-I. Hirai, Y. Nagashima, T. Fujimoto, Y. Tabuse, K.J. Kemphues, and S. Ohno. 1998. J. Cell Biol. 143:95–106), this suggests a ubiquitous role for aPKC in establishing cell polarity in multicellular organisms. Here, we show that the overexpression of a dominant-negative mutant of aPKC (aPKCkn) in MDCK II cells causes mislocalization of ASIP/PAR-3. Immunocytochemical analyses, as well as measurements of paracellular diffusion of ions or nonionic solutes, demonstrate that the biogenesis of the tight junction structure itself is severely affected in aPKCkn-expressing cells. Furthermore, these cells show increased interdomain diffusion of fluorescent lipid and disruption of the polarized distribution of Na+,K+-ATPase, suggesting that epithelial cell surface polarity is severely impaired in these cells. On the other hand, we also found that aPKC associates not only with ASIP/PAR-3, but also with a mammalian homologue of C. elegans PAR-6 (mPAR-6), and thereby mediates the formation of an aPKC-ASIP/PAR-3–PAR-6 ternary complex that localizes to the apical junctional region of MDCK cells. These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells.

scholarly journals Die Kaliumhydrogenphosphat-induzierte Nephropathie des Hundes. I. Pathogenese der Tubulusatrophiee [Potassium Hydrogen Phosphate Induced Nephropathy in the Dog. I. Pathogenesis of Tubular Atrophy—author's trans.]

1980 ◽  
Vol 17 (6) ◽  
pp. 699-719 ◽  
Author(s):  
P. Schneider ◽  
G. Pappritz ◽  
R. Müller-Peddinghaus ◽  
M. Bauer ◽  
H. Lehmann ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Tubular Epithelial Cells ◽  
Beagle Dogs ◽  
Lysosomal Degradation ◽  
Tubular Basement Membrane ◽  
Tubular Atrophy ◽  
Study Results

A nephropathy with severe tubular atrophy was observed in Beagle dogs after oral administration of K2HPO4 for 14 or 38 weeks. We describe the complete lysosomal degradation of atrophying tubular epithelial cells. During two experiments of 14 and 38 weeks duration, respectively, a total of 15 Beagle dogs received 0.8 g K2HPO4/kg body weight daily with their food. All dogs were examined clinically at regular intervals. Renal biopsies were taken in the fourth week from beagles of the 14-week study. Results were compared with those of control dogs. At the end of the experiments the animals were killed and necropsies done. Different stains and histochemical reactions were applied to paraffin sections of the kidneys. Acid phosphatase and β-glucuronidase were found on cryostat sections. Kidneys fixed by perfusion of five Beagles from the 38-week study and three Beagles of the 14-week study, and from five control dogs, were examined electron microscopically. Ultrahistochemically, acid phosphatase was demonstrated. Clinically, the dogs in both experiments vomited, were cachectic, and had elevated creatinine and blood urea nitrogen. Morphologically, qualitatively identical changes were seen, but the renal damage was most marked at 38 weeks. There were disseminated tubular atrophy (usually of the proximal tubules), focal scar tissue and nephrocalcinosis. The following pathogenesis was established for the lesions of the proximal tubule: Tubular atrophy begins with loss of differentiation of epithelial cells. Enzyme histochemistry, ultrahistochemistry and electron microscopy show an increase in autophagic vacuoles and autophagolysosomes. The lysosomal bodies showing fusion enclose large parts of the cytoplasm as the process continues. Complete lysosomal degradation of epithelial cells and extrusion of large lysosomes into the tubular lumen follow. After complete enzymatic digestion of the intratubular detritus, the residue is empty, convoluted and collapsed tubular basement membrane. Atrophic tubular epithelial cells have many organelle-free zones at their base, which contain fine filamentous material resembling that of the basement membrane. The degradation processes described here may explain why clinically the urinary sediment contains few cylinders and epithelial cells and why proteinuria decreases significantly toward the end of the experiment. So far, it is not clear whether the tubular basement membrane is synthesized by the tubular cells, by fibroblasts or by both cell types. The presence of basement membrane-like material in tubular epithelial cells and in parietal epithelial cells of the glomerulus favors the view that epithelial cells produce the basement membranes and that increased production of basement membrane-like material is a sign of loss of differentiation.

scholarly journals Developmental switch of intestinal antimicrobial peptide expression

2008 ◽  
Vol 205 (1) ◽  
pp. 183-193 ◽  
Author(s):  
Sandrine Ménard ◽  
Valentina Förster ◽  
Michael Lotz ◽  
Dominique Gütle ◽  
Claudia U. Duerr ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
High Performance ◽  
Bacterial Colonization ◽  
Paneth Cell ◽  
Active Form ◽  
Constitutive Expression ◽  
Postnatal Period ◽  
Enteric Infection ◽  
Immune Effector ◽  
Developmental Switch

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.

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