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Originally published In Press as doi:10.1074/jbc.M206689200 on August 5, 2002
J. Biol. Chem., Vol. 277, Issue 41, 38571-38578, October 11, 2002
Functional Linkage between the Endoplasmic Reticulum Protein
Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle
Cells*
Edward F.
Rocnik ,
Eric
van der Veer,
Henian
Cao,
Robert A.
Hegele§, and
J. Geoffrey
Pickering§¶
From the Robarts Research Institute (Vascular Biology Group),
London Health Sciences Center, Departments of Medicine (Cardiology),
Biochemistry, Medical Biophysics, University of Western Ontario,
London N6A 5K8, Canada
Hsp47 is a heat stress protein that interacts
with procollagen in the lumen of the endoplasmic reticulum, which is
vital for collagen elaboration and embryonic viability. The precise
actions of Hsp47 remain unclear, however. To evaluate the effects of
Hsp47 on collagen production we infected human vascular smooth muscle cells (SMCs) with a retrovirus containing Hsp47 cDNA. SMCs
overexpressing Hsp47 secreted type I procollagen faster
than SMCs transduced with empty vector, yielding a greater accumulation
of pro 1(I) collagen in the extracellular milieu. Interestingly, the
amount of intracellular pro 1(I) collagen was also increased. This
was associated with an unexpected increase in the rate of pro 1(I) collagen chain synthesis and 2.5-fold increase in pro 1(I) collagen mRNA expression, without a change in fibronectin expression. This amplification of procollagen expression, synthesis, and secretion by
Hsp47 imparted SMCs with an enhanced capacity to elaborate a fibrillar
collagen network. The effects of Hsp47 were qualitatively distinct
from, and independent of, those of ascorbate and the combination of
both factors yielded an even more intricate fibril network. Given the
in vitro impact of altered Hsp47 expression on procollagen
production, we sought evidence for interindividual variability in Hsp47
expression and identified a common, single nucleotide polymorphism in
the Hsp47 gene promoter among African Americans that significantly
reduced promoter activity. Together, these findings indicate a
novel means by which type I collagen production is regulated by the
endoplasmic reticulum constituent, Hsp47, and suggest a potential basis
for inherent differences in collagen production within the population.
*
This work was supported by grants from the Canadian
Institutes of Health Research (MT11715) and Heart and Stroke Foundation of Canada (T4458).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by a Heart and Stroke Foundation Studentship Award.
§
Career Investigators of the Heart and Stroke Foundation of Ontario.
¶
To whom correspondence should be addressed: London Health
Sciences Center, 339 Windermere Rd., London, Ontario N6A 5A5. Tel.: 519-663-3973; Fax: 519-434-3278; E-mail: gpickering@robarts.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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