Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts

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...

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Main Authors: Keittisak Suwan, Kanyamas Choocheep, Sonoko Hatano, Prachya Kongtawelert, Koji Kimata, Hideto Watanabe
Format: Journal
Published: 2018
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-593872018-09-10T03:14:36Z Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts Keittisak Suwan Kanyamas Choocheep Sonoko Hatano Prachya Kongtawelert Koji Kimata Hideto Watanabe Biochemistry, Genetics and Molecular Biology 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. 2018-09-10T03:14:36Z 2018-09-10T03:14:36Z 2009-03-27 Journal 1083351X 00219258 2-s2.0-67649760194 10.1074/jbc.M806927200 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67649760194&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/59387
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Keittisak Suwan
Kanyamas Choocheep
Sonoko Hatano
Prachya Kongtawelert
Koji Kimata
Hideto Watanabe
Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
description 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.
format Journal
author Keittisak Suwan
Kanyamas Choocheep
Sonoko Hatano
Prachya Kongtawelert
Koji Kimata
Hideto Watanabe
author_facet Keittisak Suwan
Kanyamas Choocheep
Sonoko Hatano
Prachya Kongtawelert
Koji Kimata
Hideto Watanabe
author_sort Keittisak Suwan
title Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
title_short Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
title_full Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
title_fullStr Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
title_full_unstemmed Versican/PG-M assembles hyaluronan into extracellular matrix and inhibits CD44-mediated signaling toward premature senescence in embryonic fibroblasts
title_sort versican/pg-m assembles hyaluronan into extracellular matrix and inhibits cd44-mediated signaling toward premature senescence in embryonic fibroblasts
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67649760194&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/59387
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