INT232826

Context Info Confidence 0.68 First Reported 2008 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 26 Total Number 32 Disease Relevance 14.24 Pain Relevance 0.48

structural molecule activity (Krt18) microtubule organizing center (Krt18) cytoplasm (Krt18)

Anatomy Link Frequency liver 5 hepatocytes 2 filament 1 4T1 1 epithelial cells 1 Krt18 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 72 92.88 Bile 57 84.96 Potency 19 84.96 metalloproteinase 3 82.72 fibrosis 162 81.92 alcohol 57 41.92 Paracetamol 78 36.56 cytokine 8 27.28 dexamethasone 4 19.80 imagery 40 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 338 100.00 Adhesions 8 100.00 Cancer 1358 99.48 Liver Disease 289 99.40 Ovarian Cancer 164 99.38 Aging 42 97.24 Injury 179 96.44 Apoptosis 438 95.12 Stress 344 94.36 Nash(non-alcoholic Steatohepatitis) 133 94.00

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Mutation

Event

Anatomy

Negation

Speculation

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Disease term

Figure 2I shows as an example the FACS-based quantitation of Krt18 expression in G-2 cells at passage 20, indicating transition towards a mesenchymal differentiation state.

Gene_expression (expression) of Krt18

1) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920333 Disease Relevance 0.08 Pain Relevance 0

In early passages the majority of the G-2 cells expressed both Krt14 (Figure 2G) and Krt18 intermediate filament proteins (Figure 2H); however the usual co-polymerization partner of Krt14, the Krt5 protein, was not detectable by a specific antibody (data not shown).

Gene_expression (expressed) of Krt18 in filament

2) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920333 Disease Relevance 0 Pain Relevance 0

In subsequent passages slight variations in the individual expression levels of Krt14 and Krt18 (data not shown) and a significant fluctuation in the number of cytokeratin-expressing cells ranging from 40 to 70% were observed.

Gene_expression (expression) of Krt18

3) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920333 Disease Relevance 0.07 Pain Relevance 0

As visualized by IF-staining, the G-2 cell pattern of cytokeratin expression was reproduced in G-2 cell derived clones (Figure S1A–B; shown as example for clones G-2C9 and G-2C11), although according to qPCR analysis the relative levels of Krt14 and Krt18 gene expression varied markedly between clones (Figure S1C–D).

Gene_expression (expression) of Krt18

4) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920333 Disease Relevance 0.14 Pain Relevance 0

The few Thy1high cells expressing Krt18 may represent either contaminating cells, or cells which are in process of transition towards the Thy1low-state (see below).

Gene_expression (expressing) of Krt18

5) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920333 Disease Relevance 0.18 Pain Relevance 0

Both OSE and EOC tumors are characterized by the expression of different keratins such as KRT7, KRT8 and KRT18.

Gene_expression (expression) of KRT18 associated with cancer and ovarian cancer

6) Confidence 0.66 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2467432 Disease Relevance 0.80 Pain Relevance 0

Stronger expression of Krt7 is observed in TOV-1946 and TOV-2223G was the only cell line that expressed Krt18 and Krt8.

Gene_expression (expressed) of Krt18

7) Confidence 0.66 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2467432 Disease Relevance 0.94 Pain Relevance 0

In order to determine if our cell lines presented these EOC markers, we monitored protein expression of Krt7, Krt8 and Krt18 by western blot.

Gene_expression (expression) of Krt18 associated with ovarian cancer

8) Confidence 0.66 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2467432 Disease Relevance 0.78 Pain Relevance 0

The epithelial characteristics of the cell lines were also verified by the expression of Krt18 and Krt8, which are also markers of epithelial cells.

Gene_expression (expression) of Krt18 in epithelial cells

9) Confidence 0.66 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2467432 Disease Relevance 0.93 Pain Relevance 0

Several pathogenic mechanisms were implicated in this process (Fig. 4; Dobson 2004):1.Enhanced oxidative stress2.Disproportional K8/K18 expression together with keratin modifications3.Chaperone dysfunction4.Elevated p62 levels5.Insufficient protein degradation

Gene_expression (expression) of K18

10) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.22 Pain Relevance 0.08

MDBs also arise in cell culture after transfection with K8/K18, ubiquitin, and p62.

Gene_expression (transfection) of K18

11) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Abstract Doc Link PMC2386529 Disease Relevance 1.00 Pain Relevance 0.04

Keratins are major constituents of MDBs and both altered K8/K18 expression and keratin modification seems to affect MDB formation (Zatloukal et al. 2007; Ku et al. 2007).

Gene_expression (expression) of K18

12) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.78 Pain Relevance 0

Griseofulvin/DDC feeding leads to rapid induction of K8/K18 expression with disproportional K8 > K18 levels (Denk et al. 2000).

Gene_expression (expression) of K18

13) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.71 Pain Relevance 0

Dysbalanced K8/K18 expression precedes MDB formation, likely increases keratin misfolding and predisposes to posttranslational modifications, which may interfere with keratin refolding and/or repair.

Gene_expression (expression) of K18

14) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.30 Pain Relevance 0

However, one important caveat is the fact, that K8/K18/K19 are expressed in most simple epithelial cells and are therefore not liver-specific (Moll et al. 1982; Ku et al. 1999).

Gene_expression (expressed) of K18 in liver

15) Confidence 0.64 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.31 Pain Relevance 0

In cell culture experiments, protein aggregates resembling MDBs formed only after p62 co-transfection, but not when K8, K18, and ubiquitin were transfected alone or in combination (Stumptner et al. 2007).

Gene_expression (transfected) of K18

16) Confidence 0.55 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.17 Pain Relevance 0

Adult hepatocytes are unique among simple epithelial cells in that they express exclusively K8 and K18, whereas other glandular epithelia exhibit a more complex keratin expression pattern (Omary et al. 2002; Ku et al. 2007).

Gene_expression (express) of K18 in hepatocytes

17) Confidence 0.55 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.65 Pain Relevance 0.04

The K8/K18 within MDBs exhibit increased ?

Gene_expression (/) of K18

18) Confidence 0.55 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.09 Pain Relevance 0

For example, “simple” (i.e., single layered) epithelia, as found in digestive organs, express K8 together with variable levels of K7, K18, K19, and K20 depending on the tissue (Moll et al. 1982; Ku et al. 1999; Coulombe and Omary 2002; Ku et al. 2007).

Gene_expression (levels) of K18

19) Confidence 0.55 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.05 Pain Relevance 0

The K8/K18 within MDBs exhibit increased ?

Gene_expression (The) of K18

20) Confidence 0.55 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.09 Pain Relevance 0

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