The alpha-L-Rhamnose recognizing lectin site of human dermal fibroblasts functions as a signal transducer: modulation of Ca2+ fluxes and gene expression.
An alpha-l-Rhamnose specific lectin site was described on human skin keratinocytes and fibrobasts. The addition of Rhamnose-rich oligo- and polysaccharides (RROPs) to fibroblasts has been shown to stimulate cell proliferation and increase extracellular matrix biosynthesis, suggesting that this lectin site functions as a "true" receptor transmitting messages to the cell interior. It was confirmed here that addition of the Rhamnose-rich polysaccharide, RROP-1, to normal human dermal fibroblasts (NHDFs) and human endothelial cells produced a dose-dependent stimulation of the calcium-signaling pathway, inducing fast and transient increases in Ca2+ influx and intracellular free Ca2+ level. The Rhamnose-rich oligosaccharide RROP-3 as well as l-Rhamnose alone were also able to trigger similar intracellular free Ca2+ concentration increases in NHDFs. Moreover, the recording of the RROP-1-induced modification of the gene-expression profile in fibroblasts showed that this polysaccharide triggered a down-regulation of the expression of several growth factors, adhesion molecules and extracellular matrix proteins involved in pro-tumoral activity and/or fibrotic processes. These results further support the hypothesis of a receptor function for the Rhamnose-recognizing lectin site in fibroblasts. Anti-fibrotic and anti-tumoral potential of RROP-1 remains to be further explored.
Faury
Gilles
G
Laboratoire Physiopathologies vasculaires: interactions cellulaires, signalisation et vieillissement, iRTSV-APV, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. Gilles.Faury@ujf-grenoble.fr
Ruszova
E
E
Molinari
J
J
Mariko
B
B
Raveaud
S
S
Velebny
V
V
Robert
L
L
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009844:Oligosaccharides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D012210:Rhamnose / Q000378:metabolism*; D012867:Skin / Q000166:cytology*; D014471:Umbilical Veins / Q000166:cytology
D015220:Calcium Channels; D037102:Lectins; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D012210:Rhamnose; D002118:Calcium