SMAD3 functions as a transcriptional repressor of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc.

ABSTRACT: The goal of this investigation was to study the regulation of acid-sensing ion channel (ASIC)3 expression by TGFbeta in the nucleus pulposus cells of the intervertebral disc. Analysis of human nucleus pulposus tissue indicated decreased ASIC3 and elevated TGFbeta expression in the degenerate state. In a parallel study, treatment of nucleus pulposus cells with TGFbeta resulted in decreased expression of ASIC3 mRNA and protein. Suppression of ASIC3 promoter activity was evident when the nucleus pulposus cells were treated with TGFbeta or co-transfected with the constitutively active ALK5 or a smad3 construct. On the other hand, co-transfection of dominant negative smad3 or smad7 restored ASIC3 promoter activity. We validated the role of smad3 in controlling ASIC3 expression using cells deriv

SUBMITTER: Uchiyama Y 

PROVIDER: S-EPMC2684157 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature