Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/59387
Title: Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
Authors: Keittisak Suwan
Kanyamas Choocheep
Sonoko Hatano
Prachya Kongtawelert
Koji Kimata
Hideto Watanabe
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 27-Mar-2009
Abstract: Versican/PG-M is a large chondroitin sulfate proteoglycan of the extracellular matrix which interacts with hyaluronan at the N-terminal G1 domain, composed of A, B, and B′ subdomains. Recently, we generated knock-in mice Cspg23/3, whose versican, without the A subdomain, has decreased hyaluronan (HA) binding affinity, thereby exhibiting reduced deposition of versican in the extracellular matrix. Here, we show that the Cspg23/3 fibroblasts within 20 passages proliferate more slowly and acquire senescence. Whereas the extracellular matrix of the wild type fibroblasts exhibited a network structure of hyaluronan and versican, that of the Cspg23/3 fibroblasts exhibited ∼35 and ∼85% deposition of versican and HA, without such a structure. The Cspg23/3 fibroblasts showed a substantial increase of ERK1/2 phosphorylation and expression of senescence markers p53, p21, and p16. Treatment of wild type fibroblasts with hyaluronidase and exogenous hyaluronan enhanced ERK1/2 phosphorylation, and treatment with an anti-CD44 antibody that blocks HA-CD44 interaction inhibited the phosphorylation. These results demonstrate that versican is essential for matrix assembly involving hyaluronan and that diminished versican deposition increases free hyaluronan fragments that interact with CD44 and increase phosphorylation of ERK1/2, leading to cellular senescence. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67649760194&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/59387
ISSN: 1083351X
00219258
Appears in Collections:CMUL: Journal Articles

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