title: KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization.
abstract: Hyaluronan (HA) has an extraordinarily high turnover in physiological tissues, and HA degradation is accelerated in inflammatory and neoplastic diseases. CD44 (a cell surface receptor) and two hyaluronidases (HYAL1 and HYAL2) are thought to be responsible for HA binding and degradation; however, the role of these molecules in HA catabolism remains controversial. Here we show that KIAA1199, a deafness gene of unknown function, plays a central role in HA binding and depolymerization that is independent of CD44 and HYAL enzymes. The specific binding of KIAA1199 to HA was demonstrated in glycosaminoglycan-binding assays. We found that knockdown of KIAA1199 abolished HA degradation by human skin fibroblasts and that transfection of KIAA1199 cDNA into cells conferred the ability to catabolize HA in an endo-β-N-acetylglucosaminidase-dependent manner via the clathrin-coated pit pathway. Enhanced degradation of HA in synovial fibroblasts from patients with osteoarthritis or rheumatoid arthritis was correlated with increased levels of KIAA1199 expression and was abrogated by knockdown of KIAA1199. The level of KIAA1199 expression in uninflamed synovium was less than in osteoarthritic or rheumatoid synovium. These data suggest that KIAA1199 is a unique hyaladherin with a key role in HA catabolism in the dermis of the skin and arthritic synovium.
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics, Inc., Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan. yoshida.hiroyuki@kanebocos.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Aya
authors.initials: A
authors.lastname: Nagaoka
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kusaka-Kikushima
authors.forename: Megumi
authors.initials: M
authors.lastname: Tobiishi
authors.forename: Keigo
authors.initials: K
authors.lastname: Kawabata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sayo
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Enomoto
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D058851:GPI-Linked Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006025:Glycosaminoglycans / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D058105:Polymerization; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; D058851:GPI-Linked Proteins; D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D011506:Proteins; D006820:Hyaluronic Acid; C473096:Hyal2 protein, human; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase