Peptide RL‐QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds. Issue 4 (23rd March 2023)

• Record Type: Journal Article
• Authors: Wu, Yutong; Wang, Ying; Fu, Zhe; Sun, Huiling; Liu, Yixiang; Li, Chao; Wang, Yinglei; Liu, Naixin; Huang, Yubing; Yin, Saige; Guo, Kun; Feng, Chengan; Tang, Jing; He, Li; Yang, Ying; Yang, Xinwang
• Is Part Of: FASEB journal. Volume 37:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-23
• Subjects: diabetes -- epidermal nerve regeneration -- RL‐QN15 -- sensory function recovery; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201798RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post‐traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL‐QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full‐thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL‐QN15 treatment. Furthermore, RL‐QN15 promoted the proliferation, migration, and axonal length of neuron‐like PC12 cells, which was likely associated with activation of the phosphatidylinositol‐3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL‐QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL‐QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL‐QN15 peptide‐based therapeutics against diabetic skin wounds. Abstract : In the current study, localized treatment with RL‐QN15 accelerated the healing of full‐thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL‐QN15 treatment. Furthermore, the activation of PI3K/Akt signaling pathway plays an important role in the promotion of IENF regeneration by RL‐QN15.