Nrf2 Mediated Heme Oxygenase-1 Activation Contributes to Diabetic Wound Healing – an Overview

Abstract

Diabetic wound healing is a complicated procedure because hyperglycemia changes the various stages of wound healing. In type 2 diabetes mellitus (T2DM), oxidative stress is proven to be a critical factor in causing non-healing wounds and aggravating the inflammatory phase, resulting in the amputation of lower limbs in T2DM patients. This makes scientists figure out how to control oxidative stress and chronic inflammation at the molecular level. Nuclear factor erythroid 2- related factor 2 (Nrf2) releases antioxidant proteins to suppress reactive oxygen species (ROS) activation and inflammation. The current review discusses the role of Nrf2 in improving diabetic wound healing by reducing the production of ROS and thus reducing oxidative stress, as well as inhibiting nuclear factor kappa B (NF-kB) dissociation and nuclear translocation, which prevents the release of inflammatory mediators and increases antioxidant protein levels, thereby improving diabetic wound healing. As a result, the researcher will be able to find a more effective diabetic wound healing therapy.

Real‐time OXPHOS capacity analysis in wounded skin from diabetic mice: A pilot study

“…31 Alterations of mitochondrial function and the increased ROS generation negatively impact recovery, maintaining the wound in a prolonged inflammatory phase, further impairing the healing process. 7,35 The overproduction of mtROS also contributes to impaired keratinocyte mitochondrial function under high glucose conditions. 15 Moreover, our previous work indicated that mitochondrial remodelling is important in skin wound healing progression and it is impaired under diabetic conditions, contributing to deficient wound healing in a preclinical diabetes mouse model.…”

“…5 In addition, high levels of reactive oxygen species (ROS) are also observed in wounds under diabetic conditions, 4,6 aggravating the inflammatory phase. 7 Therefore, much effort has been undertaken to understand the pathogenesis and repair wound healing under diabetes conditions, and to develop novel therapeutics targeting oxidative stress and inflammation, to treat DFUs. [6][7][8] Wound healing impairment is equally prevalent under either type one or type two diabetes, and the mechanisms of tissue repair involved are similar.…”

“…15 Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the cellular antioxidant response, has been shown to improve wound healing by ameliorating diabetes-mediated oxidative stress and inflammation in STZ-induced diabetes. 7,8 Alterations in the mitochondrial respiratory states have not been addressed in the context of skin wound healing under diabetes. High-resolution respirometry (HRR) is a valuable tool in mitochondrial bioenergetics, which evaluates mitochondrial function, that is, this technique assesses mitochondrial quality independent of mitochondrial density.…”

“…DM impairs all phases of wound healing 4 mainly by stalling the wound healing progression in the inflammatory phase due to the high production of pro‐inflammatory cytokines 5 . In addition, high levels of reactive oxygen species (ROS) are also observed in wounds under diabetic conditions, 4,6 aggravating the inflammatory phase 7 . Therefore, much effort has been undertaken to understand the pathogenesis and repair wound healing under diabetes conditions, and to develop novel therapeutics targeting oxidative stress and inflammation, to treat DFUs 6–8 .…”

“…Under high glucose (HG) conditions, mouse keratinocytes (JB6) have demonstrated increases in: mitochondrial ROS (mtROS) production, mitochondrial DNA (mtDNA) damage, deregulation of mtDNA‐encoded OXPHOS subunits, inflammatory response and apoptosis via stress signalling pathway, as well as decreased antioxidant capacities 15 . Activation of the nuclear factor erythroid 2‐related factor 2 (Nrf2), a master regulator of the cellular antioxidant response, has been shown to improve wound healing by ameliorating diabetes‐mediated oxidative stress and inflammation in STZ‐induced diabetes 7,8 …”