The Anoxic Fibroblast Response Is an Early-Stage Wound Healing Program

Anderson, Garth R.; Volpe, Carmine; Russo, C.; Stoler, Daniel L.; Miloro, Scott M.

doi:10.1006/jsre.1995.1221

Cited by 15 publications

(13 citation statements)

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“…Increased secretion might be due to a change in protein sorting that helps the cell to overcome the stress. The increase in pCD secretion in oxidative stress is in accordance with an earlier report where high expression of pCD has been shown as an anoxic response protein in healing wounds (Anderson et al, 1995).…”

Section: Discussionsupporting

confidence: 92%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.

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Section: Discussionsupporting

confidence: 92%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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“…Our results now show that p53 is involved in regulating the G2/M transition in response to genotoxic stress. In particular, the p53-dependent inhibition of mitotic entry when DNA synthesis is blocked probably re¯ects a physiologically important stress response, perhaps required to avoid premature mitotic entry when DNA synthesis is arrested transiently, for example, by UV damage during S phase, or by hypoxia when rapidly growing cells outrace their blood supply or during wound healing (Anderson et al, 1995). In addition, an ecient block to mitotic entry in cells that have synthesized DNA under unfavorable conditions is likely to be important in preventing the propagation of damaged DNA.…”

Section: Discussionmentioning

confidence: 99%

p53 inhibits entry into mitosis when DNA synthesis is blocked

Taylor

Agarwal

et al. 1999

Oncogene

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Human and mouse ®broblasts with normal p53 fail to enter mitosis when DNA synthesis is blocked by aphidicolin or hydroxyurea. Isogenic p53-null ®broblasts do enter mitosis with incompletely replicated DNA, revealing that p53 contributes to a checkpoint that ensures that mitosis does not occur until DNA synthesis is complete. When treated with N-(phosphonacetyl)-Laspartate (PALA), which inhibits pyrimidine nucleotide synthesis, leading to synthesis of damaged DNA from highly unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA replication, but cells with wild-type p53 do not, revealing that p53 also mediates a checkpoint that monitors the quality of newly replicated DNA.

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“…The high metabolic demand predicts a predominantly glycolytic metabolism, a situation seen during wound repair in an essentially anoxic environment 19. Increased activities of enzymes such as glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and mitochondrial cytochrome oxidase within inflamed synovia demonstrate increased glycolytic activity 20.…”

Section: Rheumatoid Synovium Is Chronically Hypoxicmentioning

confidence: 99%