G-CSF Administration Accelerates Cutaneous Wound Healing Accompanied With Increased Pro-Hyp Production In db/db Mice

Objective: Impaired wound healing in diabetic patients is a clinical concern. However, exacerbation factors in diabetic wounds are still not clear. Inflammatory cell infiltrates after skin wounding and subsequent healing responses were investigated using diabetic mice. Methods: Granulocyte colony-stimulating factor (G-CSF), neutrophil infiltration and peptides from degraded collagen in wounded tissue were examined using db/db and wild-type mice. Results: The collagen peptides Pro-Hyp and Hyp-Gly in wounded tissue were quantified. G-CSF was transiently secreted from wounded tissue immediately after excision and then appeared in peripheral blood. G-CSF levels were significantly lower in db/ db mice than in wild-type mice, and neutrophil infiltration into the granulation tissue was lower in db/db mice. In wound tissue, only Pro-Hyp increased during the 7-day study, and Pro-Hyp levels were significantly lower in db/db mice. Wound closure was severely impaired in db/db mice. However, topical recombinant human G-CSF (rhG-CSF) administration accelerated healing, accompanied with increased neutrophil infiltration and Pro-Hyp production. Conclusion: The results show that decreased G-CSF secretion in wound tissue may trigger delayed healing in diabetic mice and that topical rhG-CSF administration increased Pro-Hyp production and accelerated healing. Therefore, G-CSF-induced Pro-Hyp may play an important role in wound healing.