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J. Cell Biol.,
Volume 140, Number 3, February 9, 1998 709-719
B in Human Fibroblasts: Role in Integrin
2 Gene Expression and Tissue Remodeling


* Department of Dermatology, School of Medicine, State University of New York, Stony Brook, New York 11794-8165; and Normal adult human dermal fibroblasts
grown in a three-dimensional collagen lattice increase
mRNA level of collagen receptor integrin subunit
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110
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-
B (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-
B family, and the degradation
of an NF-
B inhibitor protein, I
B-
. The inhibition of
NF-
B activity by SN50, a peptide inhibitor targeted at
nuclear translocation of NF-
B, significantly reduced
the induction of integrin
2 mRNA and protein by the
collagen lattice. A region located between
549 and
351 bp in the promoter of integrin
2 gene conferred
the inducibility by three-dimensional collagen lattice.
The presence of either SN50 or I
B-
32, 36, a stable mutant of I
B-
, abrogated this inducibility, indicating that the activation of integrin
2 gene expression was
possibly mediated by NF-
B through this region. Although there were three DNA-protein binding complexes forming in this region that are sensitive to the inhibition of NF-
B nuclear translocation, NF-
B was
not directly present in the binding complexes. Therefore, an indirect regulatory mechanism by NF-
B in integrin
2 gene expression induced by three-dimensional
collagen lattice is suggested. The involvement of NF-
B
in reorganization and contraction of three-dimensional
collagen lattice, a process that requires the presence
of abundant integrin
2
1, was also examined. The inhibition of NF-
B activity by SN50 greatly blocked the
contraction, suggesting its critical role in not only the
induction of integrin
2 gene expression by three-
dimensional collagen lattice, but also
2
1-mediated tissue-remodeling process.
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