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Published on: February 17, 2023
Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in
Zhifang Zheng1,2,3, Yu Wan1,2, Yishu Liu2,4
1The Graduate School of Southern Medical University, Guangzhou, China.
Abstract:
Previous studies focused on the effects of sympathetic denervation with 6-hydroxydopamine (6-OHDA) on nondiabetic wounds, but the effects of 6-OHDA on diabetic wounds have not been previously reported. In this study, treated mice received intraperitoneal 6-OHDA, and control mice received intraperitoneal injections of normal saline. Full-thickness wounds were established on the backs of mice. The wounds were sectioned (four mice per group) for analysis at 2, 5, 7, 10, 14, 17, and 21 days after injury. The wound areas in the control group were larger than those in the treatment group. Histological scores for epidermal and dermal regeneration were reduced in the 6-OHDA-treated group on day 21. The mast cells (MCs) in each field decreased after sympathectomy on days 17 and 21. The expression levels of norepinephrine, epidermal growth factor (EGF), interleukin-1 beta, NG2 proteoglycan, and desmin in the treatment group were less than those in the control group. In conclusion, 6-OHDA delays reepithelialization during wound healing in diabetic mice by decreasing EGF, but increases wound contraction by reducing IL-1β levels and the number of MCs. Besides, 6-OHDA led to reduced pericyte proliferation in diabetic wounds, which might explain the vascular dysfunction after sympathetic nerve loss in diabetic wounds.
Insights
Sympathetic denervation using 6-hydroxydopamine (6-OHDA) in diabetic mice delayed wound healing by reducing epidermal growth factor (EGF). However, it increased wound contraction by decreasing interleukin-1 beta (IL-1β) and mast cells.
Area of Science:
- Wound healing research
- Diabetic complications
- Autonomic nervous system function
Background:
- Previous research on sympathetic denervation (6-hydroxydopamine or 6-OHDA) effects on wound healing primarily focused on non-diabetic models.
- The impact of 6-OHDA on wound healing in the context of diabetes remained largely unexplored.
- Diabetic wounds are known for impaired healing processes, necessitating investigation into factors influencing them.
Purpose of the Study:
- To investigate the effects of sympathetic denervation via 6-OHDA administration on diabetic wound healing.
- To analyze the impact of 6-OHDA on key molecular and cellular components involved in the wound healing cascade in diabetic mice.
- To elucidate the mechanisms by which 6-OHDA influences reepithelialization, wound contraction, and vascular function in diabetic wounds.
Main Methods:
- Diabetic mice were treated with intraperitoneal injections of 6-hydroxydopamine (6-OHDA), while control mice received saline.
- Full-thickness wounds were surgically induced on the dorsum of the mice.
- Wound tissues were collected at multiple time points (2, 5, 7, 10, 14, 17, and 21 days) for histological and molecular analysis, including quantification of mast cells and expression levels of norepinephrine, EGF, IL-1β, NG2 proteoglycan, and desmin.
Main Results:
- Wound areas were smaller in the 6-OHDA treated group compared to controls.
- Histological scores indicated reduced epidermal and dermal regeneration in 6-OHDA treated mice by day 21.
- A decrease in mast cells, norepinephrine, epidermal growth factor (EGF), interleukin-1 beta (IL-1β), NG2 proteoglycan, and desmin was observed in the 6-OHDA group. Notably, 6-OHDA delayed reepithelialization (linked to decreased EGF) but enhanced wound contraction (linked to reduced IL-1β and mast cells) and reduced pericyte proliferation.
Conclusions:
- 6-hydroxydopamine (6-OHDA) treatment delays reepithelialization in diabetic mouse wounds, primarily by decreasing epidermal growth factor (EGF) expression.
- Conversely, 6-OHDA promotes wound contraction through the reduction of interleukin-1 beta (IL-1β) levels and mast cell counts.
- Sympathetic denervation in diabetic wounds leads to reduced pericyte proliferation, potentially contributing to observed vascular dysfunction.
