Modulation of fibroblast proliferation by oxygen free radicals
Biochemical JournalPublished 1 February 1990Open access
George A.C. Murrell, M. J. O. Francis, L. L. Bromley
Citations624
SJR quartileQ1
SJR score2.06
SNIP0.98
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Evidence is presented that oxygen free radicals can both stimulate and inhibit proliferation of cultured human fibroblasts, and that fibro Blasts themselves release superoxide (O2.-) free radicals, which provide a very fast, specific and sensitive trigger for fibroblast proliferation.
Abstract
The major unexplained phenomenon in fibrotic conditions is an increase in replicating fibroblasts. In this report we present evidence that oxygen free radicals can both stimulate and inhibit proliferation of cultured human fibroblasts, and that fibroblasts themselves release superoxide (O2.-) free radicals. Fibroblasts released O2.- in concentrations which stimulated proliferation, a finding confirmed by a dose-dependent inhibition of proliferation by free radical scavengers. Oxygen free radicals released by a host of agents may thus provide a very fast, specific and sensitive trigger for fibroblast proliferation. Prolonged stimulation may result in fibrosis, and agents which inhibit free radical release may have a role in the prevention of fibrosis.
Keywords
Medicine
New England Journal of MedicineOxygen-Derived Free Radicals in Postischemic Tissue Injury
5,441 Citations1985Franklin H. Epstein, Joe M. McCord
It is now clear that oxygen-derived free radicals play an important part in several models of experimentally induced reperfusion injury, and Dysfunction induced by free radicals may be a major component of ischemic diseases of the heart, bowel, liver, kidney, and brain.
PubMedDupuytren's contracture: fibroblast contraction? An ultrastructural study.
505 Citations1972Giulio Gabbiani, Guido Majno
It is suggested that the nodules of the palmar and plantar aponeurosis in Dupuytren's disease and Ledderhose's disease are fibroblasts that have modulated into contractile cells (myofibroblast), and that their contraction plays a role in the pathogenesis of the contracture observed clinically.
FEBS LettersAllopurinol and oxypurinol are hydroxyl radical scavengers
393 Citations1987P.Christopher Moorhouse, Martin Grootveld +3 more
The protective actions of allopurinol against reperfusion damage after hypoxia need not be entirely due to xanthine oxidase inhibition.
Arthritis & RheumatismEffect of oxygen‐derived free radicals on hyaluronic acid
364 Citations1980Robert A. Greenwald, Wai W. Moy
Generation of superoxide by leukocytes in vivo may account for the loss of synovial fluid viscosity that accompanies inflammatory joint disease.
Biochemical JournalCell killing and DNA damage by hydrogen peroxide are mediated by intracellular iron
335 Citations1984A C Mello Filho, Maria E. Hoffmann +1 more
These results, taken together with previous findings, indicate that the DNA damage is produced by hydroxyl radicals formed when H2O2 reacts with chromatin-bound Fe2+ and that this damage is responsible for the killing effect.
PubMedThe primary localization of free radical generation after anoxia/reoxygenation in isolated endothelial cells.
283 Citations1987Roman E. Ratych, Rumiana S. Chuknyiska +1 more
These experiments establish the essential components of free radical generation at reperfusion to be localized within the isolated endothelial cell in the absence of neutrophils or parenchymal cells.
American Journal of Physiology-Gastrointestinal and Liver PhysiologyConversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation
282 Citations1988Dale A. Parks, Tyisha Williams +1 more
These results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemIA.
PubMedQuantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes.
265 Citations1975Weening Rs, Ron Wever +1 more
It is proposed that the extra oxygen consumed in the respiratory burst is first reduced to O2-, possibly by ascorbate, before being converted to H2O2 during the phagocytic process.
Biochimica et Biophysica Acta (BBA) - General SubjectsThe autoxidation of glyceraldehyde and other simple monosaccharides under physiological conditions catalysed by buffer ions
218 Citations1984Paul J. Thornalley, Simon P. Wolff +2 more
Inspecting of a wide range of carbonyl compounds showed that the monosaccharide moiety -CH(OH)-C- is conserved in carbonyL compounds reactive towards autoxidation, indicating that the ability to form an ene-diol is a prerequisite to monosACcharide Autoxidation.
Journal of Bone and Joint SurgeryBiochemical changes in the collagen of the palmar fascia in patients with Dupuytrenʼs disease.
197 Citations1981D Brickley-Parsons, M J Glimcher +3 more
It is proposed that the gross contracture (shortening) of the palmar fascia in Dupuytren's disease is due to an active cellular process that progressively draws the distal extremities of the affected tissue closer together at the same time that the original tissue is being replaced.
Journal of Cellular PhysiologySuperoxide anion release by human endothelial cells: Synergism between a phorbol ester and a calcium ionophore
165 Citations1986Tsukasa Matsubara, Morris Ziff
Arthritis & RheumatismOxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes
162 Citations1986Harald Burkhardt, Melanie Schwingel +3 more
In further studies, activated polymorphonuclear leukocyte-collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency, which may be relevant to pathophysiologic states such as rheumatoid arthritis.
American Journal of Physiology-Gastrointestinal and Liver PhysiologyMechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney
148 Citations1988T.Gregory McKelvey, M. Höllwarth +4 more
Rat liver and kidney were found to produce significant amounts of DTT-reversible XO during normothermic global ischemia, suggesting that endogenous XO may also participate in the damage process independent of any conversion.
The Journal of Experimental MedicineDifferential effects of hydrogen peroxide on indices of endothelial cell function.
138 Citations1984Ann Ager, John L. Gordon
It is concluded that H2O2 has substantial effects on endothelial physiology at doses up to 3,000-fold lower than those which induce cytotoxicity.
BMJFree radicals and Dupuytren's contracture.
96 Citations1987George A.C. Murrell, M. J. O. Francis +1 more
A greater potential for hypoxanthine-xanthine oxidase generated oxygen free radical formation in Dupuytren's contracture than in control palmar fascia is suggested, as allopurinol binds to xanthine oxidation and prevents release of free radicals.
DifferentiationImmunological Identification and Determination of Xanthine Oxidase in Cells and Tissues
51 Citations1982Gerda Bruder, Hans Heid +2 more
The distribution of xanthine oxidase protein was determined in a selection of bovine cell cultures and tissues using an ultrasensitive enzymic radioimmunoassay and all fractions tested were found to contain some enzyme protein, which might reflect a specific function in the secretion of milk lipids.
Calcified Tissue InternationalThe effect of bone cell stimulatory factors can be measured with thymidine incorporation only under specific conditions
41 Citations1986J. Edward Puzas, John S. Brand
Under specific conditions, a 100% stimulation in thymidine incorporation by a mitogenic factor can be caused by as little as a 10% increase in the number of DNA synthesizing cells.
Archives of Oral BiologyRabbit cranial suture fibroblasts under tension express a different collagen phenotype
40 Citations1982Murray C. Meikle, Joan K. Heath +2 more
It is proposed that the biomechanical environment of a connective tissue cell is an important determinant of the type of collagen synthesized, and that the effect is likely to be an indirect one by virtue of its influence on the metabolic activity of the cells.
PubMedInhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide.
30 Citations1984Sem H. Phan, Joseph C. Fantone
Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities, which implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites.
PubMedInhibition of fibroblast chemotaxis by superoxide dismutase.
25 Citations1987Franz Wach, R. Hein +2 more
It is concluded that superoxide in small amounts is involved in the mechanism of fibroblast chemotaxis and superoxide dismutase may, therefore, reduce fibroblasts migration into sites of injury or inflammation.
Thrombosis ResearchStimulation of endothelial cells by protease activity in commercial preparations of xanthine oxidase
18 Citations1984Ann Ager, D.J. Wenham +1 more
These results emphasise the practical point that studies on the effects of commercial xanthine oxidase preparations on endothelial cells must take account of their trypsin-like activity as well as their capacity to generate oxygen products.
Biochemical JournalVitamin A effects on UMR 106 osteosarcoma cells are not mediated by specific cytosolic receptors
11 Citations1985Richard O. C. Oreffo, Jennifer Francis +1 more
Retinol and retinoic acid at 20 microM altered cell morphology and inhibited cell proliferation of UMR 106 osteosarcoma cells in culture and no specific cytosolic binding proteins for retinol could be detected.