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.
Wiedmaier
Nina
N
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Elfriede-Aulhorn-Str. 6, D-72076 Tübingen, Germany.
Müller
Steffen
S
Köberle
Martin
M
Manncke
Birgit
B
Krejci
Juliane
J
Autenrieth
Ingo B
IB
Bohn
Erwin
E
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D055513:Connective Tissue Growth Factor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000502:physiology; D055515:Cysteine-Rich Protein 61; D013293:Enterococcus faecalis; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D004927:Escherichia coli Infections / Q000503:physiopathology; D016908:Gram-Positive Bacterial Infections / Q000503:physiopathology; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007555:Isoxazoles / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D011422:Propionates / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000502:physiology*; D013203:Staphylococcal Infections / Q000503:physiopathology; D015009:Yersinia Infections / Q000503:physiopathology*; D015008:Yersinia enterocolitica
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D001426:Bacterial Proteins; C501848:CCN1 protein, human; C491850:CCN1 protein, mouse; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D017077:Culture Media, Conditioned; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007555:Isoxazoles; D008055:Lipids; D011422:Propionates; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; C116117:YopT protein, Yersinia; D055513:Connective Tissue Growth Factor; D003546:Cysteine Endopeptidases