Evidence for a role of collagen synthesis in arterial smooth muscle cell migration.

Rocnik, Edward; Chan, Bosco M.C.; Pickering, J. Geoffrey

doi:10.1172/jci1025

Cited by 124 publications

(95 citation statements)

References 60 publications

(46 reference statements)

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“…Western Blot Analysis of Hsp47 and Type I Collagen ExpressionAnalysis of type I collagen and Hsp47 expression was determined by Western blot analysis, as described (29). Briefly, cells and conditioned media were harvested in the presence of 0.1 mM phenylmethylsulfonyl fluoride and 10 g/ml leupeptin.…”

Section: Methodsmentioning

confidence: 99%

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Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells

Rocnik¹,

Veer

Cao

et al. 2002

Journal of Biological Chemistry

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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.

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Section: Methodsmentioning

confidence: 99%

“…For this, we have used human vascular smooth muscle cells (SMCs), which are critical to the elaboration of collagen in the vessel wall (29,30). This allowed us to evaluate the response to elevated levels of Hsp47 in the context of a fully functional pathway for procollagen biosynthesis.…”

mentioning

confidence: 99%

Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells

Rocnik¹,

Veer

Cao

et al. 2002

Journal of Biological Chemistry

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“…Migration speed of SMCs was determined by digital time-lapse video microscopy, as described previously (16,27). Cells were plated on cul-FIG.…”

Section: Methodsmentioning

confidence: 99%

Cell Surface-bound Collagenase-1 and Focal Substrate Degradation Stimulate the Rear Release of Motile Vascular Smooth Muscle Cells

Li¹,

Chow

Pickering

2000

Journal of Biological Chemistry

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To migrate in the vessel wall, smooth muscle cells (SMCs) must contend with abundant type I collagen. We investigated the mechanisms used by human SMCs to efficiently migrate on type I collagen, following stimulation with fibroblast growth factor-2 (FGF-2). FGF-2-stimulated migration was inhibited by a hydroxamic acid inhibitor of matrix metalloproteinases and by a neutralizing anti-collagenase-1 antibody. Moreover, migration speed of SMCs plated on mutant collagenase-resistant type I collagen was not increased by FGF-2. Time-lapse video analysis of unstimulated SMCs migrating on collagen revealed discrete phases of leading edge membrane extension and rear retraction, the latter often after rupture of an elongated tail. FGF-2 stimulation yielded a more synchronous, gliding motion with a collagenase-1-mediated decrease in tail ripping. Surface labeling of SMCs with biotin followed by immunoprecipitation revealed that a proportion of active collagenase-1, expressed in response to FGF-2, was bound to the plasma membrane. Pericellular collagen substrate cleavage was verified by immunostaining for neoepitopes generated by collagenase-1 action and was localized to discrete zones beneath the cell tail and the leading edge. These results identify a novel mechanism by which SMC migration on collagen is enhanced, whereby rear release from the substrate is orchestrated by the localized actions of membrane-bound collagenase-1. Migration of vascular smooth muscle cells (SMCs)1 is an important feature of arterial diseases such as atherosclerosis (1). In response to signals within the diseased vessel wall, SMCs translocate from the arterial media to the intima, or from one region in the intima to another, where they accumulate and elaborate extracellular matrix (ECM). These processes can lead to narrowing of the vascular lumen and organ ischemia.In order to migrate in the vessel wall, SMCs must contend with the dense ECM. There is good evidence that SMC migration and vascular lesion formation are accompanied by expression of ECM-degrading enzymes, including matrix metalloproteinases (MMPs, matrixins) (2-6). Furthermore, SMC migration in the artery wall has been inhibited by infusion of a broad spectrum MMP inhibitor (5) and delivery of tissue inhibitor of metalloproteinase-2 (7). These data thus support a role for ECM proteolysis in SMC translocation, although it is not yet established which ECM components need to be degraded.Fibrillar type I collagen is a dominant ECM protein of both the normal and diseased artery wall (8, 9). Unlike many ECM constituents, type I collagen is susceptible to degradation by only a few enzymes. Of these, collagenase-1 (MMP-1), which has been detected in human atherosclerotic lesions (2-4), appears to be the principal SMC-derived collagenolytic enzyme, although collagenase-3 (MMP-13) (10) and cathepsin K (11, 12) may also participate. Collagenase-1 degrades type I collagen by cleaving a single site in the triple helical domain to yield a 3/4 N-terminal fragment and 1/4 C-terminal fragment. At phys...

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“…In vitro, treatment of cells with collagen synthesis inhibitors prevented the formation of focal adhesions and the assembly of actin stress fibers, and attenuated SMC migration. 43 The deficits in migration persisted regardless of whether SMCs were plated on wells pre-coated with collagen types I, III, or IV, showing that the cells did not merely migrate across a pre-formed matrix, but modified the matrix by depositing new collagen. The types of newly synthesized collagens were not identified in this study, but it is tempting to speculate that type VIII collagen was one of them.…”

Section: Collagen Remodeling Smooth Muscle Cell Proliferation and MImentioning

confidence: 97%

Collagens in the progression and complications of atherosclerosis

et al. 2009

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Collagens constitute a major portion of the extracellular matrix in the atherosclerotic plaque, where they contribute to the strength and integrity of the fibrous cap, and also modulate cellular responses via specific receptors and signaling pathways. This review focuses on the diverse roles that collagens play in atherosclerosis; regulating the infiltration and differentiation of smooth muscle cells and macrophages; controlling matrix remodeling through feedback signaling to proteinases; and influencing the development of atherosclerotic complications such as plaque rupture, aneurysm formation and calcification. Expanding our understanding of the pathways involved in cell-matrix interactions will provide new therapeutic targets and strategies for the diagnosis and treatment of atherosclerosis.

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Evidence for a role of collagen synthesis in arterial smooth muscle cell migration.

Cited by 124 publications

References 60 publications

Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells

Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells

Cell Surface-bound Collagenase-1 and Focal Substrate Degradation Stimulate the Rear Release of Motile Vascular Smooth Muscle Cells

Collagens in the progression and complications of atherosclerosis

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