2002 Fiscal Year Final Research Report Summary
Apoptotic pathways in keloids; involvement of activated caspase and cytochrome c release during the apoptosis of keloid fibroblasts
| Project/Area Number |
13670191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | School of Medicine, Toho University |
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Principal Investigator |
AKASAKA Yoshikiyo Second Department of Pathology, School of Medicine, Toho University, Associate Professor, 医学部, 助教授 (60202511)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Toshiharu Second Department of Pathology, School of Medicine, Toho University, Professor, 医学部, 教授 (30101893)
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| Project Period (FY) |
2001 – 2002
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| Keywords | keloids / Apoptosis / caspase / cytochrome-c / Wound healing |
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| Research Abstract |
Apoptosis has a role in normal and pathologic forms of healing. However, the role of apoptosis and the mechanisms responsible for the induction of apoptosis in keloids remain unclear. This study aimed to examine the apoptotic properties in keloids using anti-cleaved caspase antibodies and investigate whether the caspase-9/mitochondrial pathway is involved in the apoptotic induction of keloid fibroblasts. The number of fibroblasts positive for TUNEL, activated caspase-9 or -3 was relatively low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of these caspase-positive fibroblasts and the TUNEL-positive fibroblasts were observed, suggesting that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts in vivo. Cultured keloid fibroblast lines showed apoptosis after serum deprivation, and the activation of caspase-9 and -3 was detected in all the lines with serum deprivation for 3
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or 4 hours, as confirmed by the detection of the 37 kd caspase-9 cleaved fragment and the 17 kd caspase-3 cleaved fragment. Furthermore, the manifestation of apoptosis was blocked by a caspase-9 inhibitor (Ac-LEHD-CHO), indicating that the activation of caspase-9 is necessary for the execution of apoptosis of keloid fibroblasts. Cytochrome c was also detectable in the cytosolic fraction of the lines after serum deprivation for 3 or 4 hours, indicating the close relationship between caspase-9 activation and cytochrome c release in response to serum deprivation in keloid fibroblasts. Because of the lack of change in the level of apoptosis protease activating factor-1 in all the lines, the activation of caspase-9 and -3 might be dependent on cytochrome c release from the mitochondria. These results indicate that cytochrome c release can underlie regulation of apoptosis in keloid fibroblasts through caspase-9 and -3 activation and suggest that the predisposed apoptosis contributes to the pathogenesis of keloid formation. Less
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Research Products
(4 results)
