Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment

Yur Ren Kuo, Wen Sheng Wu, Seng Feng Jeng, Hui Chen Huang, Kuender D. Yang, Justin Michael Sacks, Feng Sheng Wang

Research output: Contribution to journalArticle

Abstract

Background and Objectives: Flashlamp pulsed-dye lasers (PDLs) revealed effective regression or arrest in patients with keloids in our clinical studies [Kuo YE et al., Laser Surg Med 2004;34:104-108]. In this study, we further investigated whether the induction of keloid regression seen with PDL treatment through activation in mitogen-activated protein (MAP) kinase and caspase promotes cell apoptosis and reduces fibroblast proliferation. Study Design/Materials and Methods: Keloid tissues were obtained from 10 patients with intralesional or punch biopsies prior to and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14 J/cm2)]. Prior to and after PDL treatments, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining and fragmented caspase-3 expression. MAP kinase activation as represented by extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK) expression of keloid tissues was investigated by immunohistochemical (IHC) staining, respectively. Results: IHC staining indicated that PCNA expression of fibroblasts was significantly reduced in keloid tissue after PDL irradiation. TUNEL assay revealed lower apoptotic cells expression in the keloid tissue prior to laser treatment. Following laser treatment, apoptotic cells with relatively strong DNA damage and fragmentation were seen in all keloid biopsy samples, especially in the keloid fibroblast population. The activation of ERK and p38 MAP kinase increased significantly in keloid tissue after PDL treatment. JNK was shown to be unchanged. Conclusions: The PDL treatment is shown to induce keloid regression through suppression of keloid fibroblast proliferation, induction of apoptosis, and upregulation of ERK and p38 MAP kinase activity.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalLasers in Surgery and Medicine
Volume36
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Dye Lasers
Keloid
Extracellular Signal-Regulated MAP Kinases
Phosphotransferases
Fibroblasts
Apoptosis
Therapeutics
Lasers
Proliferating Cell Nuclear Antigen
p38 Mitogen-Activated Protein Kinases
Staining and Labeling
Mitogen-Activated Protein Kinases
Biopsy
DNA Nucleotidylexotransferase
JNK Mitogen-Activated Protein Kinases
DNA Fragmentation
Caspases
Transferases
Caspase 3
DNA Damage

Keywords

  • Apoptosis
  • Keloids
  • Mitogen-activated protein kinase
  • Pulsed-dye laser

ASJC Scopus subject areas

  • Surgery

Cite this

Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment. / Kuo, Yur Ren; Wu, Wen Sheng; Jeng, Seng Feng; Huang, Hui Chen; Yang, Kuender D.; Sacks, Justin Michael; Wang, Feng Sheng.

In: Lasers in Surgery and Medicine, Vol. 36, No. 1, 01.2005, p. 31-37.

Research output: Contribution to journalArticle

Kuo, Yur Ren ; Wu, Wen Sheng ; Jeng, Seng Feng ; Huang, Hui Chen ; Yang, Kuender D. ; Sacks, Justin Michael ; Wang, Feng Sheng. / Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment. In: Lasers in Surgery and Medicine. 2005 ; Vol. 36, No. 1. pp. 31-37.
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abstract = "Background and Objectives: Flashlamp pulsed-dye lasers (PDLs) revealed effective regression or arrest in patients with keloids in our clinical studies [Kuo YE et al., Laser Surg Med 2004;34:104-108]. In this study, we further investigated whether the induction of keloid regression seen with PDL treatment through activation in mitogen-activated protein (MAP) kinase and caspase promotes cell apoptosis and reduces fibroblast proliferation. Study Design/Materials and Methods: Keloid tissues were obtained from 10 patients with intralesional or punch biopsies prior to and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14 J/cm2)]. Prior to and after PDL treatments, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining and fragmented caspase-3 expression. MAP kinase activation as represented by extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK) expression of keloid tissues was investigated by immunohistochemical (IHC) staining, respectively. Results: IHC staining indicated that PCNA expression of fibroblasts was significantly reduced in keloid tissue after PDL irradiation. TUNEL assay revealed lower apoptotic cells expression in the keloid tissue prior to laser treatment. Following laser treatment, apoptotic cells with relatively strong DNA damage and fragmentation were seen in all keloid biopsy samples, especially in the keloid fibroblast population. The activation of ERK and p38 MAP kinase increased significantly in keloid tissue after PDL treatment. JNK was shown to be unchanged. Conclusions: The PDL treatment is shown to induce keloid regression through suppression of keloid fibroblast proliferation, induction of apoptosis, and upregulation of ERK and p38 MAP kinase activity.",
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T1 - Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment

AU - Kuo, Yur Ren

AU - Wu, Wen Sheng

AU - Jeng, Seng Feng

AU - Huang, Hui Chen

AU - Yang, Kuender D.

AU - Sacks, Justin Michael

AU - Wang, Feng Sheng

PY - 2005/1

Y1 - 2005/1

N2 - Background and Objectives: Flashlamp pulsed-dye lasers (PDLs) revealed effective regression or arrest in patients with keloids in our clinical studies [Kuo YE et al., Laser Surg Med 2004;34:104-108]. In this study, we further investigated whether the induction of keloid regression seen with PDL treatment through activation in mitogen-activated protein (MAP) kinase and caspase promotes cell apoptosis and reduces fibroblast proliferation. Study Design/Materials and Methods: Keloid tissues were obtained from 10 patients with intralesional or punch biopsies prior to and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14 J/cm2)]. Prior to and after PDL treatments, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining and fragmented caspase-3 expression. MAP kinase activation as represented by extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK) expression of keloid tissues was investigated by immunohistochemical (IHC) staining, respectively. Results: IHC staining indicated that PCNA expression of fibroblasts was significantly reduced in keloid tissue after PDL irradiation. TUNEL assay revealed lower apoptotic cells expression in the keloid tissue prior to laser treatment. Following laser treatment, apoptotic cells with relatively strong DNA damage and fragmentation were seen in all keloid biopsy samples, especially in the keloid fibroblast population. The activation of ERK and p38 MAP kinase increased significantly in keloid tissue after PDL treatment. JNK was shown to be unchanged. Conclusions: The PDL treatment is shown to induce keloid regression through suppression of keloid fibroblast proliferation, induction of apoptosis, and upregulation of ERK and p38 MAP kinase activity.

AB - Background and Objectives: Flashlamp pulsed-dye lasers (PDLs) revealed effective regression or arrest in patients with keloids in our clinical studies [Kuo YE et al., Laser Surg Med 2004;34:104-108]. In this study, we further investigated whether the induction of keloid regression seen with PDL treatment through activation in mitogen-activated protein (MAP) kinase and caspase promotes cell apoptosis and reduces fibroblast proliferation. Study Design/Materials and Methods: Keloid tissues were obtained from 10 patients with intralesional or punch biopsies prior to and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14 J/cm2)]. Prior to and after PDL treatments, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining and fragmented caspase-3 expression. MAP kinase activation as represented by extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK) expression of keloid tissues was investigated by immunohistochemical (IHC) staining, respectively. Results: IHC staining indicated that PCNA expression of fibroblasts was significantly reduced in keloid tissue after PDL irradiation. TUNEL assay revealed lower apoptotic cells expression in the keloid tissue prior to laser treatment. Following laser treatment, apoptotic cells with relatively strong DNA damage and fragmentation were seen in all keloid biopsy samples, especially in the keloid fibroblast population. The activation of ERK and p38 MAP kinase increased significantly in keloid tissue after PDL treatment. JNK was shown to be unchanged. Conclusions: The PDL treatment is shown to induce keloid regression through suppression of keloid fibroblast proliferation, induction of apoptosis, and upregulation of ERK and p38 MAP kinase activity.

KW - Apoptosis

KW - Keloids

KW - Mitogen-activated protein kinase

KW - Pulsed-dye laser

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