Expression of genes coding for proteoglycans and Wilms' tumour susceptibility gene 1 (WT1) by variously differentiated benign human mesothelial cells

Our plain-English summary of Expression of genes coding for proteoglycans and Wilms' tumour susceptibility gene 1 (WT1) by variously differentiated benign human mesothelial cells, by M. Gulyás, K. Dobra, A. Hjerpe (Differentiation; Research in Biological Diversity, 1999).

The study

• Authors: M. Gulyás, K. Dobra, A. Hjerpe
• Journal: Differentiation; Research in Biological Diversity
• Published: 1999;65(2):89-96
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelial cells are of mesenchymal origin, although they also have epithelial characteristics. Such cells obtained from benign effusions are not terminally differentiated and can be kept in short-term cultures. These cultures grow with an either epithelial or fibroblast-like phenotype, a pattern which is stable through the early passages. Several factors have been associated with mesothelial differentiation. The Wilms' tumour susceptibility gene 1 (WT1) is expressed during transitions of mesenchyme to epithelial tissues, as in the embryonic kidney, and it has been suggested as a marker for the mesothelial lineage. The proteoglycans (PGs) and hyaluronan are also differentially synthesised by epithelial and fibroblastic malignant mesothelioma cells and the cell surface PGs seem to indicate phenotypic differentiation even in epithelial tumours. To investigate how the epithelial and fibroblast-like differentiation of benign mesothelial cells was correlated to WT1, PGs and hyaluronan synthase, we studied their expression by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analyses. The expressions of these genes were all associated with a variation in phenotypic differentiation. Cell lines with epithelial morphology expressed more mRNA coding for WT1 and cell surface PGs than did the fibroblastic ones, the difference being greatest for syndecan-4 and glypican. The increase in WT1-associated mRNA was about as great as that of syndecans. Fibroblast-like cells, on the other hand, expressed substantially more of the matrix PGs versican and biglycan, while decorin expression was detected in only trace amounts in both morphological phenotypes. Hyaluronan synthase varied individually between the cell lines, although epithelial cells often expressed higher levels. The results indicate that the regulation of mesothelial differentiation is multifactorial and also involves WT1 and several PGs.

In plain English

This was a laboratory study of benign mesothelial cells, the cells that line the chest and abdominal cavities. It did not study asbestos or any other exposure. The authors, at the Karolinska Institute in Sweden, grew 14 short-term cell lines from fluid collections (9 pleural, 5 ascitic) taken from patients with benign conditions. Four lines grew with an epithelial shape and 10 with a fibroblast-like shape, and these patterns stayed stable over later passages. All four epithelial lines came from pleural effusions. Using a semiquantitative gene-activity test (RT-PCR), the authors found WT1 gene activity in all lines analysed. Epithelial lines showed higher activity of WT1, syndecan-4 and glypican-1, and these differences were statistically significant. Fibroblast-like lines showed significantly more versican and biglycan. Decorin was found only in trace amounts in both types, and hyaluronan synthase varied from line to line. The authors concluded that mesothelial differentiation is multifactorial and involves WT1 and several proteoglycans. They noted that their measurements are best used semi-quantitatively.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory study of cultured human cells (cell lines grown from patient fluid samples), comparing gene expression by semiquantitative RT-PCR
• Who was studied: 14 short-term cell lines of benign mesothelial cells from effusions of patients with benign conditions (9 pleural, 5 ascitic), at Huddinge University Hospital, Karolinska Institute, Sweden; 4 grew with epithelial and 10 with fibroblast-like morphology; 10 lines (4 epithelial, 6 fibroblastic) were taken for RT-PCR. Dates are not given.
• Exposure: No asbestos or other environmental exposure was studied. The comparison was between cell lines growing with epithelial and fibroblast-like morphology.
• Main results:
  • The epithelial or fibroblast-like growth patterns stayed stable through four to six subsequent passages.
  • WT1 expression was found in all analysed cell lines. It was more pronounced in epithelial lines (relative fluorescence 1.40 plus or minus 0.14, n=4) than in fibroblast-like lines (1.08 plus or minus 0.08, n=5), a statistically significant difference.
  • Epithelial lines expressed significantly more syndecan-4 (2.25 plus or minus 0.24 vs 1.65 plus or minus 0.10 in fibroblastic lines) and glypican-1 (2.71 plus or minus 0.69 vs 1.63 plus or minus 0.22). The higher levels of the other cell surface proteoglycans in epithelial lines were not significant.
  • Syndecan-1 and syndecan-2 expression varied among the fibroblastic cell lines. Differences between the groups were not significant (syndecan-1: 1.36 plus or minus 0.15 epithelial vs 1.07 plus or minus 0.40 fibroblastic; syndecan-2: 1.28 plus or minus 0.29 vs 1.11 plus or minus 0.38).
  • Fibroblast-like lines expressed significantly more versican V0 (0.51 plus or minus 0.12 vs 0.19 plus or minus 0.05 in epithelial lines), versican V1 (0.88 plus or minus 0.33 vs 0.33 plus or minus 0.10) and biglycan (1.13 plus or minus 0.59 vs 0.35 plus or minus 0.05).
  • Decorin was detected only in trace amounts in all cell lines, whatever their shape.
  • Hyaluronan synthase mRNA varied from case to case, with a slightly higher average in the epithelial group (1.66 plus or minus 0.48 vs 1.14 plus or minus 0.17). The difference was not marked as significant.
  • All 4 epithelial cell lines came from pleural effusions with high granulocyte counts.
• The authors' conclusion: The authors concluded that the regulation of mesothelial differentiation is multifactorial and also involves WT1 and several proteoglycans.
• Limitations the authors state:
  • The relative fluorescence measurements relate to absolute amounts only within a narrow range, so they are best used semi-quantitatively.
  • There is no direct evidence as to which factors regulate whether the cells grow with an epithelial or fibroblastic shape.
  • The cell shape may relate to the disease that caused the effusion or to the source of the cells (pleura versus peritoneum).

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Fibroblast, Malignant Mesothelioma.

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