Transforming Growth Factor-β Up-regulates the β5Integrin Subunit Expression via Sp1 and Smad Signaling
作者： Chung-Fang Lai , Xu Feng , Riko Nishimura , Steven L. Teitelbaum , Louis V. Avioli
关键词:
摘要: Integrin-mediated cell-matrix interactions play important roles in regulating cell function. Since transforming growth factor-beta (TGF-beta) modulates many osteoblast activities, we hypothesized that the factor acts part by modulating integrin expression. TGF-beta increased adhesion to vitronectin and up-regulated surface level of alpha(v)beta(5) via increasing beta(5) protein synthesis a transcriptional mechanism. Promoter activity analysis demonstrated TGF-beta-responsive element resides between nucleotides -63 -44. Electrophoretic mobility shift assay immunoprecipitation/Western studies indicated nuclear complex formed using -66/-42 oligonucleotide contained both Sp1/Sp3 Smad proteins. levels were not altered, whereas TGF-beta, investigated proteins up-regulation gene activation. Co-transfection cells with promoter reporter construct expression vectors for Smad3, Smad4, Sp1 stimulatory effect TGF-beta. Furthermore, dominant negative Smad3 or Smad4 decreased abolished stimulation mutant also inhibited Thus, increases mechanisms involving transcription factors.
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