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A Three-dimensional Collagen Lattice Activates NF-κB in Human Fibroblasts: Role in Integrin α(2) Gene Expression and Tissue Remodeling
Normal adult human dermal fibroblasts grown in a three-dimensional collagen lattice increase mRNA level of collagen receptor integrin subunit α(2) (Xu, J., and R.A.F. Clark. 1996. J. Cell Biol. 132:239– 249.) and DNA binding activity of a nuclear transcription factor, NF-κB (Xu, J., and R.A.F. Clark...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140166/ https://www.ncbi.nlm.nih.gov/pubmed/9456329 |
Sumario: | Normal adult human dermal fibroblasts grown in a three-dimensional collagen lattice increase mRNA level of collagen receptor integrin subunit α(2) (Xu, J., and R.A.F. Clark. 1996. J. Cell Biol. 132:239– 249.) and DNA binding activity of a nuclear transcription factor, NF-κB (Xu, J., and R.A.F. Clark. 1997. J. Cell Biol. 136:473–483.). Here we present evidence that the collagen lattice induced the nuclear translocation of p50, one member of NF-κB family, and the degradation of an NF-κB inhibitor protein, IκB-α. The inhibition of NF-κB activity by SN50, a peptide inhibitor targeted at nuclear translocation of NF-κB, significantly reduced the induction of integrin α(2) mRNA and protein by the collagen lattice. A region located between −549 and −351 bp in the promoter of integrin α(2) gene conferred the inducibility by three-dimensional collagen lattice. The presence of either SN50 or IκB-α(32, 36), a stable mutant of IκB-α, abrogated this inducibility, indicating that the activation of integrin α(2) gene expression was possibly mediated by NF-κB through this region. Although there were three DNA–protein binding complexes forming in this region that are sensitive to the inhibition of NF-κB nuclear translocation, NF-κB was not directly present in the binding complexes. Therefore, an indirect regulatory mechanism by NF-κB in integrin α(2) gene expression induced by three-dimensional collagen lattice is suggested. The involvement of NF-κB in reorganization and contraction of three-dimensional collagen lattice, a process that requires the presence of abundant integrin α(2)β(1), was also examined. The inhibition of NF-κB activity by SN50 greatly blocked the contraction, suggesting its critical role in not only the induction of integrin α(2) gene expression by three- dimensional collagen lattice, but also α(2)β(1)-mediated tissue-remodeling process. |
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