Intracellular Degradation of Newly Synthesized Collagen

Bienkowski, Robert S.

doi:10.1016/s0174-173x(84)80008-4

Cited by 93 publications

(60 citation statements)

References 27 publications

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“…Expansion of this particular pool of procollagen could be due either to an increase in the procollagen chain synthesis rate or a decrease in intracellular degradation of nascent procollagen chains. The contribution of the latter pathway is likely small, given that significant co-translational degradation of pro␣ collagen chains has not been identified, and the proportion of the entire intracellular procollagen pool that is degraded within the cell is reported to be only 10-20% (43)(44)(45). Furthermore, addition of lysosomal and proteosome inhibitors had little effect on the procollagen transport kinetics in SMCs.…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…The presence of enclosed fibrils in recently-formed tissue suggests that remodelling involves recycling of fibrils of collagen. Such adjustment at the tissue level is distinct from the destruction of new collagen at the cellular level, which BIENKOWSKI et al (1978) andBERG andNEBLOCK (1985) demonstrated but considered too rapid to involve phagocytosis. The number of lysosomes present is compatible with both activities, and of course some lysosomes could be involved in other cellular cycles.…”

Section: Discussionmentioning

confidence: 99%

Collagen turnover in regenerating barbels of a catfish.

Whitear

1990

Archives of Histology and Cytology

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“…However, not all collagen that is produced gets incorporated into fibrillar collagen. Newly synthesized collagen can be degraded prior to being secreted by the cell or prior to being incorporated into fibrils in the ECM (10,12,13). There is some evidence to suggest that with aging there is an increase in degradation of newly synthesized collagen prior to secretion from the cell and a decrease in degradation of extracellular collagen (108).…”

Section: Collagen Turnover In the Lungmentioning

confidence: 99%

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

McKleroy

Lee

Atabai

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

211

169

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Pulmonary fibrosis is a vexing clinical problem with no proven therapeutic options. In the normal lung there is continuous collagen synthesis and collagen degradation, and these two processes are precisely balanced to maintain normal tissue architecture. With lung injury there is an increase in the rate of both collagen production and collagen degradation. The increase in collagen degradation is critical in preventing the formation of permanent scar tissue each time the lung is exposed to injury. In pulmonary fibrosis, collagen degradation does not keep pace with collagen production, resulting in extracellular accumulation of fibrillar collagen. Collagen degradation occurs through both extracellular and intracellular pathways. The extracellular pathway involves cleavage of collagen fibrils by proteolytic enzyme including the metalloproteinases. The less-well-described intracellular pathway involves binding and uptake of collagen fragments by fibroblasts and macrophages for lysosomal degradation. The relationship between these two pathways and their relevance to the development of fibrosis is complex. Fibrosis in the lung, liver, and skin has been associated with an impaired degradative environment. Much of the current scientific effort in fibrosis is focused on understanding the pathways that regulate increased collagen production. However, recent reports suggest an important role for collagen turnover and degradation in regulating the severity of tissue fibrosis. The objective of this review is to evaluate the roles of the extracellular and intracellular collagen degradation pathways in the development of fibrosis and to examine whether pulmonary fibrosis can be viewed as a disease of impaired matrix degradation rather than a disease of increased matrix production.

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Intracellular Degradation of Newly Synthesized Collagen

Cited by 93 publications

References 27 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

Collagen turnover in regenerating barbels of a catfish.

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

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