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Smad proteins differentially regulate transforming growth factor‐β‐mediated induction of chondroitin sulfate proteoglycans
Author(s) -
Susarla Bala T. S.,
Laing Eric D.,
Yu Panpan,
Katagiri Yasuhiro,
Geller Herbert M.,
Symes Aviva J.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07470.x
Subject(s) - transforming growth factor , smad , perineuronal net , microbiology and biotechnology , gene knockdown , neurite , sulfation , chondroitin sulfate proteoglycan , transforming growth factor beta , chondroitin sulfate , astrocyte , proteoglycan , biology , chemistry , chondroitin , biochemistry , glycosaminoglycan , neuroscience , central nervous system , extracellular matrix , gene , in vitro
J. Neurochem. (2011) 119 , 868–878. Abstract Traumatic injury to the CNS results in increased expression and deposition of chondroitin sulfate proteoglycans (CSPGs) that are inhibitory to axonal regeneration. Transforming growth factor‐β (TGF‐β) has been implicated as a major mediator of these changes, but the mechanisms through which TGF‐β regulates CSPG expression are not known. Using lentiviral expressed Smad‐specific ShRNA we show that TGF‐β induction of CSPG expression in astrocytes is Smad‐dependent. However, we find a differential dependence of the synthetic machinery on Smad2 and/or Smad3. TGF‐β induction of neurocan and xylosyl transferase 1 required both Smad2 and Smad3, whereas induction of phosphacan and chondroitin synthase 1 required Smad2 but not Smad3. Smad3 knockdown selectively reduced induction of chondroitin‐4‐sulfotransferase 1 and the amount of 4‐sulfated CSPGs secreted by astrocytes. Additionally, Smad3 knockdown in astrocytes was more efficacious in promoting neurite outgrowth of neurons cultured on the TGF‐β‐treated astrocytes. Our data implicate TGF‐β Smad3‐mediated induction of 4‐sulfation as a critical determinant of the permissiveness of astrocyte secreted CSPGs for axonal growth.