The Yin and Yang dualistic features of autophagy in thermal burn wound healing

Abstract

Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, “housekeeping” role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an “excessive” degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin–Yang features. Autophagy with its Yin–Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.

High-frequency Power Doppler Ultrasonography in Predicting Burn Depth: A Preliminary Case Report

“… 7 Blood vessels at burn site are dilated. 8 Furthermore, the detailed diameter of blood vessels detected by this method is unknown.…”

Systemic inflammation factors as survival prognosis markers in ovarian neoplasm and the relationship with cancer-associated inflammatory mediators—a review

“…Systemic inflammation must be interpreted as expressing the reparative response of body cells, to the signals carried by the cytokines secreted in excess, with a plurietiological determinism and over a long period of existence of the process. 15 – 20 …”

“…Systemic inflammation must be interpreted as expressing the reparative response of body cells, to the signals carried by the cytokines secreted in excess, with a plurietiological determinism and over a long period of existence of the process. [15][16][17][18][19][20] Physiopathologically, in neoplasias, inflammation has a dual determinism, being involved both in the installation and evolution of cancer, but also occurring as a possible defense reaction against the existing neoplasia. The use of the three parameters/indices/ratio NLR, PLR, and LMR as markers of systemic inflammation requires the exposure of the scientific support regarding the inflammation-neoplasia interference, at least regarding the existence of inflammation as a defense process against neoplasia and only tangentially as a process which intervenes in carcinogenesis.…”

Autophagy is the key to making chronic wounds acute in skin wound healing

“…For example, at the inflammatory stage of thermal burn wound healing, autophagic activity influenced by different levels of cytokines (notably IL1, IL6, IL10, and IL18), TNF and IFNG/IFN-γ (interferon gamma) begins to increase after 24 h but it does not reach normal levels until up to 72 h after the burn injury occurs [ 31 ]. At this stage, autophagy acts as a molecular pro-survival mechanism – as demonstrated by increased levels of biomarkers of autophagic activity, namely MAP1LC3/LC3 (microtubule associated protein 1 light chain 3; specifically membrane-bound LC3-II) and BECN1 (beclin 1) – that protects cells against stress effects, and even cell necrosis, caused by strong pro-inflammatory cytokines and/or triggered by microbial load [ 31 , 32 ].…”

“…To once again look at the effects of autophagy in thermal burn wound healing, keratinocyte growth factor-controlled differentiation at the proliferative and remodeling stages of wound healing triggers LC3 expression and autophagy initiation via the phosphoinositide 3-kinase (PI3K)-AKT (AKT serine/threonine kinase)-MTOR (mechanistic target of rapamycin kinase) signaling pathway, lysosomal enzyme activation and downstream autophagic machinery – as Atg5 -deficient keratinocytes are unable to undergo differentiation [ 31 ]. Additionally, autophagy levels increase during heat-denatured endothelial cell recovery, depending on intracellular reactive oxygen species generation and overall oxidative stress as well as subsequent initiation of autophagy through AMP-activated protein kinase/AMPK and MTOR signaling pathways resulting in enhanced angiogenesis [ 31 , 32 ].…”