Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner
Abstract
Cysteine-rich protein 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) are members of the CCN (CYR61, CTGF, nephroblastoma overexpressed gene) family and exert pleiotropic functions such as regulation of adhesion, migration, extracellular matrix deposition, or cell differentiation, and play an important role in wound healing. This study focused on the nature of the so far unknown CTGF and CYR61 mRNA expression of epithelial cells after infection with bacteria. We demonstrate that infection of epithelial cells with attenuated Yersinia enterocolitica lacking the virulence plasmid pYV leads to the expression of CYR61 and CTGF. Virulent Y. enterocolitica bearing the pYV virulence plasmid suppressed the mRNA expression of these genes. Yersinia-mediated inhibition of CTGF and CYR61 mRNA expression is partially mediated by the cysteine protease YopT. Further characterization of the Yersinia factors, which trigger CTGF and CYR61 mRNA expression, demonstrated that these factors were secreted and could be enriched in lipid extracts. Beside Yersinia, several other bacteria such as Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, or Staphylococcus aureus, as well as supernatants of these bacteria induced CTGF and CYR61 expression. Blocking experiments with the lysophosphatidic acid (LPA) receptor-specific inhibitor Ki16425 suggest a general involvement of LPA receptors in bacteria-triggered CTGF and CYR61 expression. These data suggest that LPA receptor-dependent expression of CTGF and CYR61 represents a common host response after interaction with bacteria.
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CCN1 is induced by bacterial and viral infections and by inflammatory cytokines such as IL-1 and TNF-α.
“CCN1 is also induced by bacterial and viral infections [29–32], and by inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) [33].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [30]
CCN1 expression is induced by bacterial and viral infections.
“CCN1 expression is induced by inflammatory cytokines such as IL-1 and TNF-α [33,131], as well as by bacterial and viral infections [29–32].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [30]
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References 63 · Cited by 34
- Authors
- Wiedmaier, N., Müller, S., Köberle, M., Manncke, B., Krejci, J., Autenrieth, I. B., & Bohn, E.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Corresponding author
- Bohn, Erwin
- Venue
- International Journal of Medical Microbiology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 298
- Issue
- 3-4
- Pages
- 231-243
- ISSN
- 1438-4221 (ISSN-L)
- OpenAlex
- W2036899152
- Cited by
- 34
- References
- 63
- Citations by year
- 2023: 1 · 2022: 2 · 2020: 3 · 2018: 2 · 2016: 6 · 2015: 4 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Medical Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Yersinia bacterium, plague, ectoparasites research
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- connective tissue growth factor, CYR61, CCN family, lysophosphatidic acid receptor, bacterial infection, epithelial cells, Yersinia enterocolitica, Ki16425, host response to bacteria, extracellular matrix regulation, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus
- MeSH terms
- Animals, Bacterial Proteins, Cysteine Endopeptidases, Epithelial Cells, Escherichia coli Infections, HeLa Cells, Humans, Isoxazoles, Lipids, Propionates, Pseudomonas Infections, RNA, Messenger, Staphylococcal Infections, Enterococcus faecalis, Yersinia enterocolitica, Yersinia Infections, Gram-Positive Bacterial Infections, Culture Media, Conditioned, Immediate-Early Proteins, Intercellular Signaling Peptides and Proteins, Receptors, Lysophosphatidic Acid, Mice, Connective Tissue Growth Factor, Cysteine-Rich Protein 61
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