Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene.
Cartilage intermediate layer protein (CILP) is an extracellular matrix protein abundant in cartilaginous tissues. CILP is implicated in common musculoskeletal disorders, including osteoarthritis and lumbar disc disease. Regulation of the CILP gene is largely unknown, however. We have found that CILP mRNA expression is induced by TGF-beta1 and dependent upon signaling via TGF-beta receptors. TGF-beta1 induction of CILP is mediated by Smad3, which acts directly through cis-elements in the CILP promoter region. Pathways other than Smad3 also are involved in TGF-beta1 induction of CILP. These observations, together with the finding that CILP protein binds and inhibits TGF-beta1, suggest that CILP and TGF-beta1 may form a functional feedback loop that controls chondrocyte metabolism.
Mori
Masaki
M
Laboratory for Bone and Joint Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Minato-ku, Tokyo, Japan.
Nakajima
Masahiro
M
Mikami
Yasuo
Y
Seki
Shoji
S
Takigawa
Masaharu
M
Kubo
Toshikazu
T
Ikegawa
Shiro
S
D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011755:Pyrophosphatases / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051900:Smad3 Protein / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D016326:Extracellular Matrix Proteins; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C114607:CILP protein, human; D011755:Pyrophosphatases