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Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System
Gunhyuk Park1, Dal-Seok Oh, Yong-Ung Kim
1The K-Herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
Pharmacology
|May 12, 2017
Summary
Extracellular basic pH accelerates wound healing by inducing early-stage apoptosis. This process involves the upregulation of specific apoptosis proteins and heat shock proteins (HSP) 60 and 70, particularly through the Fas/FasL pathway.
Area of Science:
- Dermatology
- Cell Biology
- Wound Healing Research
Background:
- Extracellular basic pH influences wound healing processes.
- Apoptosis modulation is critical for effective wound healing, aiding in inflammatory cell removal and scar prevention.
Purpose of the Study:
- To investigate the impact of extracellular basic pH on skin apoptosis.
- To determine the specific molecular mechanisms by which basic pH affects skin cells during wound healing.
Main Methods:
- Utilized a 3D human skin equivalent model.
- Measured apoptosis-related protein levels using an array kit.
- Detected target protein expression via immunostaining.
- Quantified lactate dehydrogenase and Annexin V levels spectrophotometrically and by fluorescence staining, respectively.
Main Results:
- Basic pH (8.40) significantly upregulated extrinsic apoptosis proteins (Fas, TRAF1, p21) and moderately upregulated intrinsic apoptosis proteins (cytochrome c, Bcl-2 family members).
- Basic pH induced heat shock proteins (HSP) 60 and 70.
- Knockdown of Fas and HSP60 significantly reduced basic pH-induced apoptosis.
Conclusions:
- Extracellular basic pH promotes early-stage apoptosis in skin.
- This effect is mediated through the Fas/FasL pathway, involving the modulation of HSP60 and HSP70.
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