Autophagy is required for the directed motility of keratinocytes driven by electric fields

Abstract

Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF‐biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Initially, we found that electrical signals directed keratinocytes to the cathode with enhanced motility parameters [i.e., trajectory distance, trajectory speed, displacement distance, and displacement speed (Td/t)] and more efficient migration (directionality and Td/t along the x axis, among others). Meanwhile, EFs induced a time‐dependent increase in autophagic activity in keratinocytes, with constant autophagic flux, accompanied by increased transcription of numerous autophagy‐related genes. Deficiency in Atg5, a key protein necessary for autophagosome formation, led to significant reduction of autophagy, which was accompanied by a substantial reduction in EF‐stimulated directed motility. These results demonstrated a causal relationship between autophagy and EF‐directed migratory speed. In addition, both cell migration under normal conditions and EF‐biased directionality were autophagy independent. Thus, our findings define autophagy as an important functional regulator of electrically enhanced directed motility, adding to a growing understanding of EFs.—Yan, T., Jiang, X., Lin, G., Tang, D., Zhang, J., Guo, X., Zhang, D., Zhang, Q., Jia, J., Huang, Y. Autophagy is required for the directed motility of keratinocytes driven by electric fields. FASEB J. 33, 3922–3935 (2019). http://www.fasebj.org

FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1‐dependent autophagy

“…A growing body of literature indicates that autophagy is a central mechanism by which various factors promote the motility of keratinocytes (Yan et al, 2019). Previous studies reported that Fgf21 deficiency impairs autophagy in several tissues, including the liver and muscle.…”

m6A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin

“…It was reported that autophagy is shown to be activated in response to glucose withdrawal via activation of PRKAA2/AMPK (protein kinase AMP-activated catalytic subunit alpha 2) and inactivation of MTOR [ 67 ]. Besides, directed migratory speed could be enhanced via inducing autophagic activity in keratinocytes driven by electric fields [ 68 ]. A recent study has also revealed the critical role of keratinocyte autophagy in facilitating wound healing via regulating CCL2 (C-C motif chemokine ligand 2) expression in a mouse model [ 18 ].…”

The establishment and development of wound repair discipline in China

“…One can build a suitable microenvironment for wound healing, one can load with stem cells and various healing promoting factors (growth factors, exosomes, etc. ), novel functional and intelligent biomimetic wound repair materials with anti-infective agents (21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”