Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury

Desmoulière, Alexis; Badid, Chérif; Bochaton‐Piallat, Marie‐Luce; Gabbiani, Giulio

doi:10.1016/s1357-2725(96)00117-3

Cited by 170 publications

(140 citation statements)

References 46 publications

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“…Apoptosis is important in the resolution phase of the normal wound healing response (9). In healthy peripheral human lung only sporadic cells undergo apoptosis.…”

mentioning

confidence: 99%

Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Maher¹,

Evans²,

Bottoms³

et al. 2010

Am J Respir Crit Care Med

172

161

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Rationale: Patients with idiopathic pulmonary fibrosis (IPF), a progressive disease with a dismal prognosis, exhibit an unexplained disparity of increased alveolar epithelial cell (AEC) apoptosis but reduced fibroblast apoptosis. Objectives: To examine whether the failure of patients with IPF to upregulate cyclooxygenase (COX)-2, and thus the antifibrotic mediator prostaglandin (PG)E 2 , accounts for this imbalance. Methods: Fibroblasts and primary type II AECs were isolated from control and fibrotic human lung tissue. The effects of COX-2 inhibition and exogenous PGE 2 on fibroblast and AEC sensitivity to Fas ligand (FasL)-induced apoptosis were assessed. Measurements and Main Results: IPF lung fibroblasts are resistant to FasL-induced apoptosis compared with control lung fibroblasts. Inhibition of COX-2 in control lung fibroblasts resulted in an apoptosis-resistant phenotype. Administration of PGE 2 almost doubled the rate of FasL-induced apoptosis in fibrotic lung fibroblasts compared with FasL alone. Conversely, in primary fibrotic lung type II AECs, PGE 2 protected against FasL-induced apoptosis. In human control and, to a greater extent, fibrotic lung fibroblasts, PGE 2 inhibits the phosphorylation of Akt, suggesting that regulation of this prosurvival protein kinase is an important mechanism by which PGE 2 modulates cellular apoptotic responses. Conclusions: The observation that PGE 2 deficiency results in increased AEC but reduced fibroblast sensitivity to apoptosis provides a novel pathogenic insight into the mechanisms driving persistent fibroproliferation in IPF.

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“…Apoptosis is important in the resolution phase of the normal wound healing response (9). In healthy peripheral human lung only sporadic cells undergo apoptosis.…”

mentioning

confidence: 99%

Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Maher¹,

Evans²,

Bottoms³

et al. 2010

Am J Respir Crit Care Med

172

161

View full text Add to dashboard Cite

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“…The most notable pathological forms of healing are hypertrophic scarring and keloid formation. During these processes of excessive scarring, it is conceivable that apoptosis cannot take place and the cells participating in granulation tissue are not eliminated (Desmouliere et al, 1997;Rockwell et al, 1989). Previous studies have suggested a potential role of apoptosis in pathological forms of healing (Desmouliere et al, 1997;Greenhalgh, 1998;Rockwell et al, 1989).…”

mentioning

confidence: 99%

“…During these processes of excessive scarring, it is conceivable that apoptosis cannot take place and the cells participating in granulation tissue are not eliminated (Desmouliere et al, 1997;Rockwell et al, 1989). Previous studies have suggested a potential role of apoptosis in pathological forms of healing (Desmouliere et al, 1997;Greenhalgh, 1998;Rockwell et al, 1989). Although conflicting result was obtained with regard to the level of apoptosis in keloid fibroblasts (Appleton et al, 1996;Saed et al, 1998), it is still uncertain how deregulation of apoptosis can lead to hypertrophic scarring or keloid formation.…”

mentioning

confidence: 99%

Enhanced Expression of Caspase-3 in Hypertrophic Scars and Keloid: Induction of Caspase-3 and Apoptosis in Keloid Fibroblasts In Vitro

Akasaka

Ishikawa

Ono

et al. 2000

Laboratory Investigation

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SUMMARY:Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and development of pathological scarring. To examine the phenomenon of apoptosis and its involvement in the process of pathological scarring, we immunohistochemically quantified differential levels of expression of caspase-3 and -2, which are activated during apoptosis in vitro, in surgical resected scar tissues. We divided 33 cases of normally healed flat scars and 18 cases of pathological scars (15 cases of hypertrophic scars and 3 cases of keloid) into three groups (S1 ϭ Ͻ10 months' duration; S2 ϭ 10 to 40 months' duration; and S3 ϭ Ͼ40 months' duration) according to the duration of scar. In all three groups examined, the semiquantitative scores for caspase-3 staining were significantly higher for the combination of hypertrophic scars and keloid as a group compared with normally healed flat scars, suggesting reduced cell survival and increased apoptotic cell death in hypertrophic scars and keloid. Apoptosis and caspase proteolytic activities were examined in vitro using two flat scar-derived fibroblast lines (FSFB-1 and -2) and two keloid-derived fibroblast lines (KFB-1 and -2). After 24 hours of serum deprivation, apoptotic cells were significantly increased in both KFB lines, whereas serum deprivation of FSFB-1 cells did not result in a significant increase in apoptotic cell number. After serum deprivation, significant increases in caspase-3 proteolytic activities were detected in both KFB lines compared with both FSFB lines. In contrast, no significant differences with caspase-8 activity were observed between similarly treated KFB and FSFB lines. Furthermore, serum deprivation-induced apoptosis of KFB-2 cells was significantly inhibited by the caspase-3 inhibitor Ac-Asp-Glu-Val-Asp-fluoromethyl ketone (DEVD-FMK), indicating that caspase-3 is important for serum deprivation-induced apoptosis in KFB-2 cells. Considering the role of caspase-3 as a key effector molecule in the execution of apoptotic stimuli, our results suggested that enhanced expression of caspase-3 in hypertrophic scars and keloid induces apoptosis of fibroblasts, which may play a role in the process of pathological scarring. (Lab Invest 2000, 80:345-357).

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“…A few studies have attempted to explain the etiology of keloids and have reported abnormalities in the regulation of apoptosis during the wound healing process. They have suggested that pathological scarring might be a consequence of the accumulation of granulation tissue as a result of defective apoptosis mechanisms [32][33][34][35] . Desmoulière et al 33 have shown that the number of apoptotic cells sharply increases as the wound closes, suggesting that apoptosis is involved in the progressive transformation of granulation tissue into scar.…”

Section: Discussionmentioning

confidence: 99%

Oxidative damage and nuclear factor erythroid 2-related factor 2 protein expression in normal skin and keloid tissue

2016

Journal of the American Academy of Dermatology

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Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury

Cited by 170 publications

References 46 publications

Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Enhanced Expression of Caspase-3 in Hypertrophic Scars and Keloid: Induction of Caspase-3 and Apoptosis in Keloid Fibroblasts In Vitro

Oxidative damage and nuclear factor erythroid 2-related factor 2 protein expression in normal skin and keloid tissue

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Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury

Cited by 170 publications

References 46 publications

Diminished Prostaglandin E2Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Diminished Prostaglandin E2Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Enhanced Expression of Caspase-3 in Hypertrophic Scars and Keloid: Induction of Caspase-3 and Apoptosis in Keloid Fibroblasts In Vitro

Oxidative damage and nuclear factor erythroid 2-related factor 2 protein expression in normal skin and keloid tissue

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Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

Diminished Prostaglandin E₂Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis