Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Keratin-18”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1986

Comparison of mouse and human keratin 18: a component of intermediate filaments expressed prior to implantation.

Keratin 18 is a type-I keratin that is found in a variety of simple epithelial tissues. In mice, the corresponding protein, called Endo B, is expressed at the 4- to 8-cell stage of mouse development and may be one of the first intermediate-filament proteins synthesized after fertilization. A cDNA clone for keratin 18, designated pK18, was isolated from a human placental cDNA library by hybridization with the mouse Endo-B probe. It was characterized by hybridization selection of RNA, translation, immunoprecipitation, Northern blotting, and sequence analysis. Synthetic T7 polymerase transcripts of the cDNA were indistinguishable in size from keratin-18 mRNA, suggesting that pK18 represents a full-length copy of the RNA. The cDNA insert is 1,428 nucleotides long and contains a single open reading frame of 1,342 nucleotides coding for 429 amino acids. The deduced amino acid sequence is 89.7% identical with that of Endo B. The only extensive difference between the two sequences is due to 9 additional amino acids being present in the last half of the N-terminal domain of keratin 18. The 38-nucleotide-long 3' noncoding region of the cDNA is 75% identical with the corresponding portion of Endo B. The 5' noncoding regions are 59% identical. The expression of keratin-18 mRNA was found to vary more than tenfold when HeLa cells and BeWo trophoblastic cells were compared.

Amino Acid Sequence↗
PubMed2026

A bireporter recombinant SARS-CoV-2 Omicron BA.5 for in vitro and in vivo studies.

The continuous emergence of variants of concern (VoCs) represents a significant challenge to effectively control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although FDA-approved vaccines and antivirals have been successfully developed and implemented for the prophylactic and therapeutic intervention of SARS-CoV-2 infection, recent VoCs could escape protection garnered by previous vaccine and antiviral approaches. Determining the efficacy of prophylactics and/or therapeutics against recent VoCs will assist in efficiently controlling currently circulating SARS-CoV-2 strains. We used our previously described bacterial artificial chromosome-based reverse genetics approach for Omicron BA.5 to generate a recombinant SARS-CoV-2 BA.5 encoding a fusion of ZsGreen to Nanoluciferase (rBA.5 ZsG-Nluc) from the locus of the viral nucleocapsid (N) protein separated by the porcine teschovirus-1 2A proteolytic cleavage site. The rBA.5 ZsG-Nluc replicates to levels comparable to recombinant BA.5 wild type (rBA.5 WT) and expresses high levels of ZsG and Nluc in cultured cells. This facilitates tracking viral infection and the identification of antivirals and neutralizing antibodies with EC50 and NT50 values, respectively, similar to those obtained with rBA.5 WT. Importantly, in Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc retains the same pathogenicity and ability to replicate in the lungs of infected mice as rBA.5 WT. Using rBA.5 ZsG-Nluc, we detected Nluc activity systemically and Nluc and ZsG expression in the lungs of infected mice using an in vivo imaging system. Our results demonstrate the feasibility of using rBA.5 ZsG-Nluc to track viral infections and identify prophylactics and therapeutics against recent SARS-CoV-2 VoCs in vitro, ex vivo, and in vivo.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 pandemic, is continually evolving to escape immunity acquired by previous natural infections or vaccinations. Moreover, recent SARS-CoV-2 variants of concern (VoCs) have acquired antiviral-resistant mutations to FDA-approved drugs. The emergence of these VoCs highlights the importance of identifying new prophylactics and therapeutics against currently circulating SARS-CoV-2 strains. We generated a recombinant bireporter Omicron BA.5 SARS-CoV-2 (rBA.5 ZsG-Nluc) that expresses reporter proteins, which are useful for cellular and whole animal studies, and has similar viral replication and pathogenicity to a wild-type recombinant Omicron BA.5 SARS-CoV-2. In Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc infection can be tracked systemically or in the lungs of infected mice using an in vivo imaging system. We establish a proof-of-concept platform of rBA.5 ZsG-Nluc in combination with an ancestral SARS-CoV-2 strain expressing mCherry to simultaneously identify antivirals and neutralizing antibodies against original and recent SARS-CoV-2 strains.

SARS-CoV-2↗
PubMedDate not supplied

Protein changes associated with ionizing radiation-induced apoptosis in human prostate epithelial tumor cells.

Ionizing radiation (IR) is an important component in the therapy of localized prostate cancer. Identification of protein alterations during IR-induced apoptosis prostate cancer cells is an important step toward understanding the new metabolic status of the dying cell. In the present study, we report changes in protein profile that define the execution phase of the apoptotic response in the in vitro model of tumorigenic radiation-transformed SV40-immortalized human prostate epithelial cells (267B1-XR), induced to undergo programmed cell death by IR. We employed an approach that involves use of analytical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) coupled with Western blotting with specific antisera. Our results point out that apoptotic cells experience significant reduction in the levels of the intermediate filament proteins, keratins-18, 19, vimentin and the associated 14-3-3 adapter proteins. At the same time, molecular chaperones such as glucose-regulated protein 94, calreticulin, calnexin, and protein disulfide isomerase exhibit marked accumulation in these dying cells. The present data indicate that apoptosis-associated processes in prostate epithelial cells include solubilization of the rigid intermediate filament network by specific proteolysis as well as increased levels of endoplasmic reticulum (ER) proteins with chaperone functions.

Apoptosis↗
PubMed1997

cDNA libraries from single human preimplantation embryos.

In this paper, the construction, evaluation, and application of cDNA libraries from eight unfertilized oocytes and single four-cell-, seven-cell-, and blastocyst-stage embryos are described. Rapid, reproducible, and efficient procedures for the construction of PCR-based cDNA libraries from fewer than 10 cells were first developed in small populations of fibroblast cells. The human embryo libraries display complexities sufficient (between 10(5) and 10(6) clones) to represent the entire active gene population at these early stages of human development. The ubiquitous cytoskeletal elements, beta-actin, keratin-18, and alpha-tubulin, were detected at the expected frequency. Sequencing of consecutively picked random clones, without selection, showed the presence of a variety of sequences, such as the human transposable element, LINE-1 and Alu repeat sequences, housekeeping genes, and tissue-specific genes, such as alpha-globin and FMR-1. In addition to cDNAs corresponding to known ESTs (expressed sequence tags) in the GenBank and dbEST databases, a high proportion of novel sequences were detected. Applications of the libraries to several areas of interest, such as expression of CpG-island-containing "tissue-specific" genes, developmental genes expressed in a stage-specific manner, and a search for monoallelic expression of imprinted genes, are described. The libraries are a valuable resource for the study of gene expression during human preimplantation development and obviate the need for research on the human embryos themselves.

Cells, Cultured↗
PubMed2001

A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans.

A novel human gene, SARM, encodes the orthologue of a Drosophila protein (CG7915) and contains a unique combination of the sterile alpha (SAM) and the HEAT/Armadillo motifs. The SARM gene was identified on chromosome 17q11, between markers D17S783 and D17S841 on BAC clone AC002094, which also included a HERV repeat and keratin-18-like, MAC30, TNFAIP1, HSPC017, and vitronectin genes in addition to three unknown genes. The mouse SARM gene was located on a mouse chromosome 11 BAC clone (AC002324). The SARM gene is 1.8 kb centromeric to the vitronectin gene, and the two genes share a promoter region that directs a high level of liver-specific expression of both the SARM and the vitronectin genes. In addition to the liver, the SARM gene was highly expressed in the kidney. A 0.4-kb antisense transcript was coordinately expressed with the SARM gene in the kidney and liver, while in the brain and malignant cell lines, it appeared independent of SARM gene transcription. The SARM gene encodes a protein of 690 amino acids. Based on amino acid sequence homology, we have identified a SAM motif within this derived protein. Structure modeling and protein folding recognition studies confirmed the presence of alpha-alpha right-handed superhelix-like folds consistent with the structure of the Armadillo and HEAT repeats of the beta-catenin and importin protein families. Both motifs are known to be involved in protein-protein interactions promoting the formation of diverse protein complexes. We have identified the same conserved SAM/Armadillo motif combination in the mouse, Drosophila, and Caenorhabditis elegans SARM proteins.

Amino Acid Motifs↗
PubMed1999

Developmental expression of specific genes detected in high-quality cDNA libraries from single human preimplantation embryos.

We describe an improved highly sensitive method for generating cDNA libraries containing a high proportion of cDNAs enriched with 5'-coding sequences from single human preimplantation embryos and a 10 week old whole foetus. The embryonic mRNA was isolated using oligo-(dT) linked to magnetic beads. First-strand cDNA synthesis was carried out directly on the bound mRNA, followed by PCR designed to amplify the cDNA molecules synthesized in their entirety. The complexities of the libraries are between 10(5) and 10(6) independent clones. The average cDNA size is 1.0 kb, and the size range is 0.5-3.0 kb. PCR analysis of the embryonic libraries for specific genes has revealed transcripts for genes known to be transcribed in preimplantation stages, such as the imprinted gene SNRPN, developmental genes WNT11, HOX, OCT-1 and the embryonic OCT-4, cytoskeletal genes keratin-18 and beta-actin, the cell cycle gene C-MOS, and housekeeping genes GAPDH and HPRT. Sequencing of random clones showed the presence of a variety of sequences, such as human chorionic gonadotrophin, ubiquitin, TFIIA, guanine nucleotide-binding protein (beta-subunit), annexin I, a gene encoding a kinesin-like protein, and TWIST, which encodes a basic helix-loop-helix (bHLH) transcription factor implicated in Saethre-Chotzen syndrome (characterized by craniofacial and limb anomalies). Approximately 40% of these randomly analysed clones were full length. In addition to cDNAs matching known ESTs (Expressed Sequence Tags) in the GenBank and dbEST databases, novel sequences were detected at a frequency of 16% of randomly picked clones. The libraries are a valuable resource, providing longer cDNAs representing genes expressed during human preimplantation development.

Actins↗
PubMed1998

The construction of cDNA libraries from human single preimplantation embryos and their use in the study of gene expression during development.

PURPOSE: The construction and application of polymerase chain reaction (PCR)-based cDNA libraries from unfertilized human oocytes and single preimplantation-stage embryos are described. The purpose of these studies is to provide a readily available resource for the study of gene expression during human preimplantation development. METHODS: Rapid, reproducible, and efficient procedures for the construction of PCR-based cDNA libraries from fewer than 10 cells were first developed in small populations of fibroblast cells. We then constructed cDNA libraries from eight unfertilized oocytes and single two-cell, -4-cell, -7-cell, and blastocyst-stage embryos. Differential display PCR using the libraries as template allows the analysis of stage-specific expression of embryonic genes. Genomic libraries are also prepared from parental samples (cumulus cells and sperm) corresponding to the individual embryo generating the cDNA library. RESULTS: The complexities (between 10(5) and 10(6) clones) of the human embryo libraries indicate that they may represent the entire active gene population at these early stages of human development. Nucleotide sequence analyses of random clones showed the presence of a variety of transcripts, such as the human transposable element. LINE-1, Alu repeat sequences, housekeeping genes, and tissue-specific genes, (e.g., alpha-globin, FMR-1, and interleukin-10). Also present at the expected frequency are the ubiquitous cytoskeletal elements, beta-actin, keratin-18, and alpha-tubulin. In addition to cDNAs corresponding to known expressed sequence tags (ESTs) in the GenBank and dbEST databases, a high proportion of novel sequences was also detected. Several cDNAs were detected only at specific stages of preimplantation development by the differential display analysis. CONCLUSIONS: PCR-based cDNA libraries from single human preimplantation embryos provide a new and important resource for the identification and study of novel genes or gene families. As such, they will increase our basic understanding of the molecular control of human development. In the clinical context, the libraries identify the time of onset of specific genes, and hence the diseases resulting from mutation of these genes, and provide information about new methods of preimplantation diagnosis. The molecular analysis of early gene transcription in human embryogenesis may be expected to lead to advances in contraception, assisted reproduction, and preimplantation genetic diagnosis.

Blastocyst↗
PubMed1995

Keratins as markers of differentiated taste cells of the rat.

Cytokeratins in taste buds were immunocytochemically evaluated with monoclonal antibodies. In each of six different epithelial sites in the rat oral cavity, intragemmal cells of taste buds were immunoreactive for keratin polypeptides 8, 18, and 19, as well as for keratin 7, which has not been previously reported in taste buds. Keratin-18-like immunoreactivity was present in fewer than half of the intragemmal cells, whereas all intragemmal cells were immunopositive for keratins 7, 8, and 19. Apart from some salivary duct cells, no other cells in the tongue were immunoreactive for any of these four keratins. Morphological and immunocytochemical profiles indicate that taste buds are islets of simple epithelium embedded in an expanse of stratified squamous epithelium. These simple epithelial cells and their keratins are nerve-dependent, since denervation eliminated all four keratins and replaced elongated taste cells of the vallate papilla with stratified squamous epithelium. We conclude that antibodies against keratins 7, 8, or 19 are useful markers for intragemmal cells in studies of taste bud development, degeneration, regeneration, turnover and tissue culture.

Animals↗
PubMed1997

Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line.

To better understand the mechanism(s) underlying lung cancer invasion and metastasis, a Transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human lung adenocarcinoma, CL1. Five sublines with progressive invasiveness, designated CL1-1, CL1-2, CL1-3, CL1-4, and CL1-5, were obtained through this in vitro selection process. Their invasive abilities through basement membrane matrix showed a 4- to 6-fold increase over that of the parental cells. Moreover, the sublines manifested an increase in their colony-forming ability on soft agar, tumorigenicity, and metastatic potency in severe combined immunodeficiency (SCID) mice. Examining the phenotypes of the cell lines revealed increased expression of 92 kD gelatinase and an increase in the cell population stained with anti-keratin-8 and -18 antibodies. Clonal isolation of anti-keratin-18-antibody-positive and -negative cell populations demonstrated a correlated enhancement of the invasiveness of these cells and their expression of keratin-18. These results support the notion that the metastatic behavior of lung cancer cells can be characterized with this in vitro system, and that the properties of these progressively invasive cancer cells can be clonally studied.

Adenocarcinoma↗
PubMed1993

Establishment and characterization of a SV40 T-antigen immortalized epithelial-like cell line derived from the newborn rat colorectum and its malignant transformation by the ras oncogene.

Epithelial-like cells from the colorectum of one-day-old newborn rats were immortalized by transfection with the simian virus 40 (SV40) T-antigen gene, and a cell line OUMS-25 was established. The cells were positive for the SV40 T-antigen, and immunoreactive to a colonic epithelial cell monoclonal antibody and a keratin-18 monoclonal antibody. Ultrastructural studies revealed the presence of microvilli on the cell surface and desmosomes between the adjacent cells. Karyotypic analysis showed that OUMS-25 cells were aneuploid. Cloning efficiency of the cells was 0.01% in soft agar. However, the cells were not tumorigenic in the syngeneic newborn rats. The cells were further transformed by transfection with the cloned activated c-Ha-ras oncogene containing a point mutation within codon 61. Characteristics of the activated-c-Ha-ras transfected cells (OUMS-25/RAS) were different in some respects from those of the parent cells (OUMS-25). OUMS-25/RAS cells demonstrated more malignant morphology, elevated cloning efficiency in soft agar, and tumorigenicity. This is the first report on the immortalization and malignant transformation of colorectal epithelial-like cells by transfection with a combination of SV40 T-antigen gene and cloned activated c-Ha-ras oncogene.

Animals↗
PubMedDate not supplied

Characterization of a rat glomerular visceral epithelial cell line.

Cultures of glomerular epithelial cells (GEC) are currently used to identify important cellular and molecular mechanisms involved in the pathogenesis of renal diseases. However, there is still controversy in the literature as to the visceral or parietal origin of cultured GEC. Our aim was to firmly establish the nature of a GEC cell line. The reactivity of cultured GEC was investigated with a large panel of mono- and polyclonal antibodies by using immunofluorescent techniques and compared with literature data on the in vivo expression of these antigens on podocytes. In addition, the podocyte specific 5A (podocalyxin), 13A and 27A (9-O-acetylated GD3) antigen expression was investigated in immuno-overlay experiments with isolated gangliosides and in immunoprecipitations with metabolically labelled cells. In general, immunoreactivities between cultured GEC and literature data on GEC in vivo expressions were similar. Important podocyte epitopes in vivo were expressed by cultured GEC such as podocalyxin, gp330 and the 13A antigen. Cultured GEC however differed from their in vivo counterparts in their expression of keratin-18, their lack of expression of pp44 and no detectable immunohistological expression of the ganglioside 9-O-acetylated GD3. Interestingly, the podocyte-specific epitope 9-O-acetylated GD3 was detected by the 27A antibodies in immuno-overlays of isolated GEC gangliosides. Moreover, by using the 27A antibody, we were able to precipitate the podocyte-specific 103-kD protein from 35S-methionine metabolically labelled GEC. From our immunohistological data together with the detectability of the 27A antigen we conclude that the cell line we use very probably originates from glomerular visceral epithelial cells.

Animals↗
PubMed2004

Keratin 8 and 18 hyperphosphorylation is a marker of progression of human liver disease.

Keratin 8 and 18 (K8/18) phosphorylation plays a significant and site-specific role in regulating keratin filament organization, association with binding proteins, and modulation of cell cycle progression. Keratin hyperphosphorylation correlates with exposure to a variety of stresses in cultured cells and in mouse models of liver, pancreatic, and gallbladder injury, and it is found in association with mouse and human Mallory bodies. We asked whether K8/18 phosphorylation correlates with human liver disease progression by analyzing liver explants and biopsies of patients with chronic noncirrhotic hepatitis C virus (HCV) or cirrhosis. We also examined the effect of HCV therapy with interleukin-10 on keratin phosphorylation. Using site-specific antiphosphokeratin antibodies we found keratin hyperphosphorylation on most K8/18 sites in all cirrhotic liver explants tested and in most liver biopsies from patients with chronic HCV infection. Immunofluorescence staining of precirrhotic HCV livers showed focal keratin hyperphosphorylation and limited reorganization of keratin filament networks. In cirrhotic livers, keratin hyperphosphorylation occurred preferentially in hepatic nodule cells adjacent to bridging fibrosis and associated with increased stress kinase activation and apoptosis. Histological and serological improvement after interleukin-10 therapy was accompanied by normalization of keratin hyperphosphorylation on some sites in 7 of 10 patients. In conclusion, site-specific keratin phosphorylation in liver disease is a progression marker when increased and a likely regression marker when decreased.

Biomarkers↗
PubMed2004

Keratin mutations and intestinal pathology.

Whilst the importance of mutations in a wide range of keratins in skin fragility disorders is now well established, there is much less evidence for simple epithelial keratin involvement in disease. Some simple epithelial keratin mutations have been reported in liver cirrhosis and pancreatitis patients, and recently mutations in the simple epithelial keratin K8 were identified in a group of patients with inflammatory bowel disease (Crohn disease or ulcerative colitis). In comparison with the mutations seen in epidermal keratins, these simple epithelial mutations would be predicted to have mild consequences, although analysis shows that they do have a distinct effect. This review article discusses the evidence that these mutations are a predisposing factor for inflammatory bowel disease.

Colon↗
PubMed2004

Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype.

In recent studies, Böcker and colleagues described a population of cells in paraffin wax sections of normal human breast that express cytokeratins (CK) 5/6 without expression of CK8/18 or smooth muscle actin (SMA). They proposed that these represent stem cells that give rise to differentiated luminal and myoepithelial cells. The data have been used to generate a model for breast cancer progression and classification with associated implications for management of pre-invasive disease. In this study, the expression of CK5/6, CK8/18, and SMA was investigated using multiple immunofluorescence on matched pairs of paraffin wax-embedded and frozen breast specimens. The staining patterns reported previously in antigen-retrieved paraffin wax-embedded sections were confirmed but no CK5/6-only cells were found in frozen sections of normal breast. There were cells with low levels of CK8/18 expression in frozen sections that may correspond to the CK8/18 'negative' cells seen in paraffin wax sections. This study brings into question the previously described profile of breast 'stem cells' based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype.

Actins↗
PubMed2004

Global proteomic approach unmasks involvement of keratins 8 and 18 in the delivery of cystic fibrosis transmembrane conductance regulator (CFTR)/deltaF508-CFTR to the plasma membrane.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF gene (cftr). Physiologically, CF is characterized by an abnormal chloride secretion in epithelia due to a dysfunction of a mutated cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a cAMP-dependent chloride channel whose most frequent mutation, deltaF508, leads to an aberrantly folded protein which causes a dysfunction of the channel. However, a growing number of reports suggest that modifier genes and environmental factors are involved in the physiology of CF. To identify proteins whose expression depends on wild-type WT-CFTR or deltaF508-CFTR, we chose a global proteomic approach based on the use of two-dimensional gel electrophoresis (2-DE) and mass spectrometry. The experiments were carried out with HeLa cells stably transfected with WT-CFTR (pTCFWT) or deltaF508-CFTR (pTCFdeltaF508). These experiments unmasked keratin 8 (K8) and 18 (K18) which were differentially expressed in pTCFWT vs. pTCFdeltaF508. An immunoblot of K18 confirmed the 2-DE results. Intracellular localization experiments of WT-CFTR, deltaF508-CFTR, K8, and K18 suggest that the expression of these proteins are linked, and that the concentrations of K8 and K18 and/or their distribution may be involved in the traffic of WT-CFTR/deltaF508-CFTR. A functional assay for CFTR revealed that specifically lowering K18 expression or changing its distribution leads to the delivery of functional deltaF508-CFTR to the plasma membrane. This work suggests a novel function of K18 in CF.

Cell Membrane↗
PubMed2004

Keratin 8/18 breakdown and reorganization during apoptosis.

Monoclonal antibodies that specifically recognize caspase cleaved K18 fragments or specific (phospho)epitopes on intact K8 and K18 were used for a detailed investigation of the temporal and causal relationship of proteolysis and phosphorylation in the collapse of the keratin cytoskeleton during apoptosis. Caspases involved in the specific proteolysis of keratins were analyzed biochemically using recombinant caspases and specific caspase inhibitors. Finally, the fate of the keratin aggregates was analyzed using the M30-ApoptoSense trade mark Elisa kit to measure shedding of caspase cleaved fragments into the supernatant of apoptotic cell cultures. From our studies, we conclude that C-terminal K18 cleavage at the (393)DALD/S site is an early event during apoptosis for which caspase 9 is responsible, both directly and indirectly by activating downstream caspases 3 and 7. Cleavage of the L1-2 linker region of the central alpha-helical rod domain is responsible for the final collapse of the keratin scaffold into large aggregates. Phosphorylation facilitates formation of these aggregates, but is not crucial. K8 and K18 remain associated in heteropolymeric aggregates during apoptosis. At later stages of the apoptotic process, that is, when the integrity of the cytoplasmic membrane becomes compromised, keratin aggregates are shed from the cells.

Apoptosis↗
PubMed2003

cDNA sequences of the authentic keratins 8 and 18 in zebrafish.

From the zebrafish Danio rerio, we have cDNA cloned and sequenced a novel type II and a novel type I keratin, termed DreK8 and DreK18, respectively. We identified DreK8/18 as the true orthologs of the human keratin pair K8/18 as follows: (i) MALDI-MS assignment to the biochemically identified K8 and K18 candidates that are co-expressed in simple epithelia and absent in epidermal keratinocytes; (ii) multiple sequence alignments and phylogenetic tree analysis, showing that DreK8, within the phylogenetic tree of type II keratins, forms a highly bootstrap-supported branch together with K8 from goldfish and rainbow trout, whereas DreK18, within the phylogenetic tree of type I keratins, groups with the K18 sequences from all other vertebrates studied; (iii) presence of a conserved motif in the tail domain of DreK8 (VxKxxETxDGxxVSESSxV) that is typical for all hitherto sequenced K8 orthologs. Moreover, several zebrafish type II keratin sequences published by other authors have now been assigned to epidermal keratins, previously identified biochemically.

Amino Acid Sequence↗
PubMed2004

Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver.

AIMS: Ductal plate malformation (DPM) is the persistence of excess of embryonic bile duct structures in the portal tracts. Most of the congenital diseases of intrahepatic bile ducts represent examples of DPM at different levels of the biliary tree. The aim of the present study was to evaluate the histopathological spectrum and immunohistochemical properties of DPM in various paediatric liver diseases and compare them with those of the normal embryonic ductal plates of human fetuses. METHODS AND RESULTS: All paediatric liver biopsies and autopsied livers of infant deaths and stillbirths over a 5-year period (between 1996 and June 2001) were subjected to histopathological examination to identify ductal plate malformations. A detailed immunohistochemical analysis was carried out in 35 cases of ductal plate malformation and 25 abortuses by using antibodies against cytokeratin (CK)7, 8, 18 and 19, CD34 and type IV collagen. Thirty-nine cases of ductal plate malformation were identified which consisted of extrahepatic biliary atresia with DPM (n = 20), isolated congenital hepatic fibrosis (n = 9), autosomal recessive polycystic kidney disease (n = 5), congenital hepatic fibrosis with autosomal polycystic kidney disease (n = 2), Caroli's syndrome (n = 2) and one case of Ivemark's syndrome. The ductal plate cells stained with CK7, 8, 18 and 19 but not with CD34. CONCLUSION: DPM was present in all intrahepatic bile duct diseases included in this study and in about 26% of cases of extrahepatic biliary atresia. The cytokeratin immunophenotype of the ductal plate in pathological conditions is similar to that of normal embryonic ductal plates of fetuses after 20 weeks of gestation.

Antigens, CD34↗