Renal dysfunction aggravated impaired cutaneous wound healing in diabetic mice

Abstract

Renal dysfunction has been associated with poor outcomes of wound healing in the diabetic population. The purpose of this study was to create an excisional wound healing model in diabetic mice with renal dysfunction to investigate the combined effects of diabetes and nephropathy on cutaneous ulcers. Renal impairment was introduced in diabetic db/db mice through unilateral nephrectomy and electrocoagulation of the contralateral kidney. Renal function was subsequently monitored with assays of blood urea nitrogen and spot urinary protein/creatinine ratio. After 8 weeks, splinted, full‐thickness excisional wounds were created on the dorsal skin and harvested on postoperative days 7 and 14 for further evaluation of wound healing. Renal injury promoted the increase of blood urea nitrogen 3 weeks after initial operation, which was maintained at double the control level throughout the study, concomitantly leading to a significant increase of spot urinary protein excretion. Diabetic mice with renal injury displayed notably impaired wound healing processes, concurrent with reductions in cellular proliferation and angiogenesis, as well as increases in M1 polarized macrophages, infiltrated neutrophils, oxidative stress, and cellular apoptosis. Furthermore, quantitative polymerase chain reaction (qPCR) results displayed corresponding changes of related genes (TNF‐α, IL‐1β, SOD2) in the wounds of renal injured db/db mice. Renal manipulation in this study accelerated the progress of renal impairment, which was demonstrated to aggravate impaired cutaneous wound healing in diabetic mice.

Scar Acceleration Method—MAC<sup>®</sup> in the Treatment of Chronic Wounds in Lymphedema: Case Report

“…Several inflammatory parameters are elevated in diabetic patients and constitute strong predictors of the development of this disease. The increase in inflammatory cytokine levels in the diabetic patient leads to microvascular complications, such as the development of nephropathy [9] [10]. Activated immune cells migrate and infiltrate kidney tissue locally, producing more inflammatory mediators and chemokines that recruit more immune cells to the kidney.…”

“…Furthermore, quantitative polymerase chain reaction (qPCR) results showed corresponding alterations of related genes (TNF-α, IL-1β, SOD2) in wounds from db/db mice with kidney injury. Renal manipulation in this study accelerated the progress of renal impairment, which has been shown to worsen impaired skin wound healing in diabetic mice leading to a significant increase in urinary protein excretion [10] [12].…”

Experimental Models to Study Skin Wound Healing with a Focus on Angiogenesis

“…The splinted full thickness model enables direct application of topical agents on the wound bed or assessment of wound healing upon systemically pharmacological treatment. In parallel to other murine wound healing models, it also allows the study of wound healing in different pathological conditions, e.g., renal dysfunction [44], using respective transgenic or knockout mice. The splinted wound model was recently applied in rats to study hypertrophic scarring [45] and to study new splint constructions [46].…”

“…The splinted full thickness model was used study the effects of recombinant myxoma virus-derived immune modulator M-T7 [49], of Babassu oil [50], of three-dimensional printed scaffolds and electrospun mats [51], of adult gingival multipotent mensenchymal stem cells [52], of induced pluripotent stem cells clay [53], of poly(lactic-co-glycolic acid) and vascular endothelial growth factor [54], and of renal dysfunction [44] on cutaneous wound healing.…”