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Induction of keratinocyte growth factor expression is reduced and delayed during wound healing in the genetically
Abstract:
We have recently demonstrated induction of expression of several members of the fibroblast growth factor family during wound healing, particularly for keratinocyte growth factor, which was more than 150-fold induced within 24 h after injury. To assess whether wound-healing disorders are associated with a defect in fibroblast growth factor regulation, we have now investigated the expression of these mitogens as well as their receptors in normal and wounded skin of genetically diabetic db/db mice, which are characterized by their impaired wound healing. We demonstrate that induction of keratinocyte growth factor expression in these mice is significantly reduced and delayed compared to normal mice. Induction of acidic fibroblast growth factor (FGF) and basic FGF expression was earlier in diabetic mice than in normal mice, but by 3 d after injury expression of these mitogens had already returned to the basal levels. In contrast, elevated levels of acidic FGF and basic FGF transcripts were detected within the first 5 d in wounds from normal mice. Thus, FGFs seem to be expressed in a limited fashion in the wound tissue of db/db mice during the period when re-epithelialization and granulation tissue formation normally occur. These findings provide an explanation for the beneficial effect of exogenous FGF in the treatment of impaired wound healing in these animals and suggest that induction of KGF early in repair may be critical for the rapid re-epithelialization in normal wound healing.
Insights
Diabetic mice show impaired wound healing due to delayed keratinocyte growth factor (KGF) induction. Fibroblast growth factors (FGFs) are also dysregulated, impacting repair processes in these models.
Area of Science:
- Wound healing research
- Molecular biology
- Genetics
Background:
- Fibroblast growth factors (FGFs) are crucial for wound repair.
- Diabetic db/db mice exhibit impaired wound healing.
- Keratinocyte growth factor (KGF) is highly induced during normal wound healing.
Purpose of the Study:
- To investigate fibroblast growth factor (FGF) and receptor expression in diabetic mouse wounds.
- To determine if impaired wound healing in db/db mice is linked to FGF dysregulation.
- To understand the role of KGF in normal versus diabetic wound repair.
Main Methods:
- Gene expression analysis of FGF family members and receptors in normal and diabetic mouse skin.
- Comparison of FGF and KGF induction patterns in wounded skin over time.
- Assessment of FGF and KGF expression in relation to wound healing stages.
Main Results:
- Diabetic mice show significantly reduced and delayed KGF induction post-injury.
- Acidic and basic FGF induction is earlier but transient in diabetic mice compared to normal mice.
- FGFs are expressed minimally in diabetic mouse wounds during critical repair phases.
Conclusions:
- Dysregulated FGF and KGF expression contributes to impaired wound healing in diabetic mice.
- Early KGF induction is critical for rapid re-epithelialization in normal wound healing.
- These findings support the therapeutic potential of exogenous FGF for treating impaired wound healing.