Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner

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.