MicroRNA-155 Inhibition Promoted Wound Healing in Diabetic Rats

Abstract

Diabetes leads to amputation in approximately 15% to 20% of patients and is associated with high morbidity and mortality. Thus, improving the quality of wound healing in this condition is essential. Diabetes is associated with acute/chronic inflammation affecting all organs especially the foot, while, inhibition of microRNA-155 (miR-155) has been reported to improve or reduce inflammatory situation. However, the role of miR-155 inhibition in promoting diabetic wound healing is not clear. To further study the potential benefit of miR-155 inhibition, a study of male Sprague-Dawley rats was conducted and diabetes was induced by injection of streptozotocin. Real-time polymerase chain reaction (PCR), hematoxylin and eosin staining and immunohistochemistry were then performed. The PCR results confirmed that miR-155 expression was lower after miR-155 inhibition on days 3, 7, and 13 (all Ps <.05). The wound healing rate between the normal glucose group (N group), diabetic PBS group (PBS group) and the topical miR-155 inhibitor group was compared. Faster healing of cutaneous wounds was observed in the miR-155 inhibitor group than in the PBS group and normal glucose group ( P < .05). In addition, downregulation of inflammatory cells, including neutrophils (MPO-positive) and macrophages (CD68-positive), and upregulation of the angiogenic protein CD31 and markers indicative of fibroblast proliferation and collagen deposition, such as collagen 1, TGF-β1, and α-SMA, were observed. These data permit the observation that miR-155 inhibition possesses the potential to reduce inflammation in acute wounds. This property may benefit the healing of diabetic foot wounds.

Mechanistic Actions of microRNAs in Diabetic Wound Healing

“…Functionally, miR-155 is important for appropriate action of a multitude of skin cells involved in wound healing, including keratinocytes [ 169 ], dermal mesenchymal stem cells [ 172 ], mast cells [ 173 ], melanocytes [ 174 ], adipocytes [ 175 ] and fibroblasts [ 176 ]. Genetic absence of miR-155 improves wound healing [ 177 ], while acute miR-155 inhibition can restore wound healing in diabetic rodent models [ 178 ].…”

Potential role of hydrogen sulfide in diabetes-impaired angiogenesis and ischemic tissue repair

“…miR-27b accelerated the wound healing process in db/db mice [ 128 ]. Inhibition of miR-155 reduced oxidative stress, increased angiogenesis and wound healing in STZ-induced diabetic rats [ 151 ]. Local administration of let-7b-containing exosomes, nanoscale membrane extracellular vesicles (30–100 nm), from LPS-primed mesenchymal stromal cells decreased inflammatory response and increased wound healing in STZ-induced diabetic mice [ 150 ].…”

MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes

“…Additionally, inhibiting miR-155 is known to reduce cell apoptosis as well as restore cardiac function in a diabetic mouse model [81]. Compromised wound healing that is notable in diabetes is also improved when miR-155 levels are suppressed [82]. Although not studied in the context of diabetic I/R injury, miR-155 inhibition protects against cardiac fibrosis in the diabetic MI mice [83].…”