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Updated: Apr 24, 2026
Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
Published on: August 21, 2020
Negative regulation of GADD34 on myofibroblasts during cutaneous wound healing
Lintao Liu1, Naomi Nishio1, Sachiko Ito1
1Department of Immunology, Nagoya University Graduate School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Abstract:
The growth arrest and DNA damage-inducible protein, GADD34, has been proved to be involved in TGF-β signaling pathway and correlates with cell death, which are two important mechanisms in regulating myofibroblast differentiation and apoptosis during tissue repair. But roles of GADD34 in myofibroblasts differentiation and apoptosis remain unknown. To investigate the function of GADD34 in these processes, we subjected WT and GADD34(-/-) mice to dermal wound healing. Here we show that GADD34(-/-) mice exhibited accelerated wound closure compared with WT mice. In addition, GADD34(-/-) mice showed increased number of myofibroblasts, elevated collagen production, and decreased cell apoptosis during wound healing. Moreover, we found that GADD34(-/-) mice showed increased phosphorylation of Smad3 and lower level of cleaved caspase-3. Thus these results indicate that GADD34 appears to suppress myofibroblast differentiation through inhibiting Smad3-dependent TGFβ signal pathway and promote its apoptosis by activating caspase-3 pathway.
Insights
Growth arrest and DNA damage-inducible protein (GADD34) suppresses myofibroblast differentiation and promotes apoptosis during wound healing. GADD34 deficiency accelerates wound closure by enhancing these processes.
Area of Science:
- Cell Biology
- Wound Healing Research
- Tissue Repair Mechanisms
Background:
- Growth arrest and DNA damage-inducible protein (GADD34) is implicated in TGF-β signaling and cell death.
- GADD34's specific roles in myofibroblast differentiation and apoptosis during tissue repair are not fully understood.
Purpose of the Study:
- To investigate the function of GADD34 in myofibroblast differentiation and apoptosis during dermal wound healing.
Main Methods:
- Utilized wild-type (WT) and GADD34 knockout (GADD34(-/-)) mice in a dermal wound healing model.
- Assessed wound closure rate, myofibroblast count, collagen production, and cell apoptosis.
- Analyzed Smad3 phosphorylation and cleaved caspase-3 levels.
Main Results:
- GADD34(-/-) mice demonstrated accelerated wound closure compared to WT mice.
- Absence of GADD34 led to increased myofibroblasts, elevated collagen, and reduced apoptosis.
- GADD34 deficiency resulted in increased Smad3 phosphorylation and decreased cleaved caspase-3.
Conclusions:
- GADD34 inhibits myofibroblast differentiation via the Smad3-dependent TGFβ pathway.
- GADD34 promotes apoptosis through the caspase-3 pathway.
- GADD34 plays a suppressive role in wound healing by limiting myofibroblast differentiation and apoptosis.
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