G1 Domain of Versican Regulates Hyaluronan Organization and the Phenotype of Cultured Human Dermal Fibroblasts

Variants of versican have wide-ranging effects on cell and tissue phenotype, impacting proliferation, adhesion, pericellular matrix composition, and elastogenesis. The G1 domain of versican, which contains two Link modules that bind to hyaluronan (HA), may be central to these effects. Recombinant hu...

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Published in:The journal of histochemistry and cytochemistry 2016-06, Vol.64 (6), p.353-363
Main Authors: Merrilees, Mervyn J., Zuo, Ning, Evanko, Stephen P., Day, Anthony J., Wight, Thomas N.
Format: Article
Language:English
Subjects:
Cell Proliferation
Cells, Cultured
Fibroblasts - cytology
Fibroblasts - drug effects
Histidine - chemistry
Humans
Hyaluronic Acid - chemistry
Hyaluronic Acid - metabolism
Protein Domains
Recombinant Proteins - pharmacology
Skin - cytology
Versicans - chemistry
Versicans - metabolism
Versicans - pharmacology
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Summary:Variants of versican have wide-ranging effects on cell and tissue phenotype, impacting proliferation, adhesion, pericellular matrix composition, and elastogenesis. The G1 domain of versican, which contains two Link modules that bind to hyaluronan (HA), may be central to these effects. Recombinant human G1 (rhG1) with an N-terminal 8 amino acid histidine (His) tag, produced in Nicotiana benthamiana, was applied to cultures of dermal fibroblasts, and effects on proliferation and pericellular HA organization determined. rhG1 located to individual strands of cell surface HA which aggregated into structures resembling HA cables. On both individual and aggregated strands, the spacing of attached rhG1 was similar (~120 nm), suggesting interaction between rhG1 molecules. Endogenous V0/V1, present on HA between attached rhG1, did not prevent cable formation, while treatment with V0/V1 alone, which also bound to HA, did not induce cables. A single treatment with rhG1 suppressed cell proliferation for an extended period. Treating cells for 4 weeks with rhG1 resulted in condensed layers of elongated, differentiated α actin-positive fibroblasts, with rhG1 localized to cell surfaces, and a compact extracellular matrix including both collagen and elastin. These results demonstrate that the G1 domain of versican can regulate the organization of pericellular HA and affect phenotype.
ISSN:0022-1554
1551-5044
DOI:10.1369/0022155416643913