Transcriptomic analysis reveals dynamic molecular changes in skin induced by mechanical forces secondary to tissue expansion

Joanna K Ledwon,Arun K Gosain,Lauren J Kelsey,Elbert E Vaca

doi:10.1038/s41598-020-71823-z

Joanna K Ledwon, Arun K Gosain + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-71823-z

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Abstract

Tissue expansion procedures (TE) utilize mechanical forces to induce skin growth and regeneration. While the impact of quick mechanical stimulation on molecular changes in cells has been studied extensively, there is a clear gap in knowledge about sequential biological processes activated during long-term stimulation of skin in vivo. Here, we present the first genome-wide study of transcriptional changes in skin during TE, starting from 1 h to 7 days of expansion. Our results indicate that mechanical forces from a tissue expander induce broad molecular changes in gene expression, and that these changes are time-dependent. We revealed hierarchical changes in skin cell biology, including activation of an immune response, a switch in cell metabolism and processes related to muscle contraction and cytoskeleton organization. In addition to known mechanoresponsive genes (TNC, MMPs), we have identified novel candidate genes (SFRP2, SPP1, CCR1, C2, MSR1, C4A, PLA2G2F, HBB), which might play crucial roles in stretched-induced skin growth. Understanding which biological processes are affected by mechanical forces in TE is important for the development of skin treatments to maximize the efficacy and minimize the risk of complications during expansion procedures.

Highlights

Tissue expansion procedures (TE) utilize mechanical forces to induce skin growth and regeneration
Our results provide key insight regarding biological processes affected by mechanical forces in TE, all of which work to simultaneously induce skin growth and maintain tissue homeostasis and integrity
Sample TE.1h.b, collected from the middle of the expander, had a shorter sample distance to the control than to the other TE samples (Fig. 1c), indicating that after 1 h of TE, skin at the apex was more strongly affected than skin in the middle of the expander. This suggests that the molecular response of skin in TE is most pronounced at the apex of the expander where the strengths of mechanical forces are the highest, and over time extends to the whole tissue

Summary

Introduction

Tissue expansion procedures (TE) utilize mechanical forces to induce skin growth and regeneration. It has been shown that when mechanical forces are applied to skin, the established state of cytoskeletal elements shifts and the position of all connected molecules and organelles are affected, changing the course of reactions that occur and resulting biochemical s ignals[19]. These features give skin an extraordinary ability to grow in response to mechanical stimulation[20], making tissue expansion (TE) ideal for obtaining extra skin in plastic and reconstructive surgery[21,22,23,24,25]. Our results provide key insight regarding biological processes affected by mechanical forces in TE, all of which work to simultaneously induce skin growth and maintain tissue homeostasis and integrity

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