Temporal Activation of Senescence-associated Secretory Proteins in a Post Burn Hypertrophic Scarring Model

Introduction. Hypertrophic scarring is the most debilitating factor that impedes the quality of life of burn survivors. Though cellular senescence was reported in burn patients’ skin, the temporal activation of cellular senescence in scar development and maintenance is unexplored. Epigenetic modifications and cellular senescence can occur prematurely following major stress (eg, burns).

Objective. To determine the role of senescence activation in the development and maintenance of hypertrophic scars post burn, the authors analyzed the temporal expression of the main senescence-associated secretory proteins (SASP) during scar development using the red Duroc pig (RDP) burn model.

Methods. The RDP burn model closely mimics human hypertrophic scarring post burn. Red Duroc skin biopsies were collected at 24 hours, and 1, 2, and 4 months post burn. The expression of messenger ribonucleic acid (mRNA) transcripts for SASPs and epigenetic modulators were compared with nonburned control biopsies.

Results. The expression of mRNA transcripts of various SASP components were upregulated at 24 hours post burn, including the cell cycle proteins p21 (P < .01) and p16 (P < .001) and the inflammatory cytokines and chemokines IL-1β (P < .01), IL-6 (P < .01), IL-8 (P < .001), MCP-1 (P < .001), TGF-β (P < .01), CXCL-10 (P < .01), and TGF-β (P < .01). The expression of mRNA transcripts for other markers of cellular senescence involved in cell motility and actin polymerization also was upregulated 24 hours post burn (CFL-1, P < .05; PAI-1 , P < .01) before returning to basal levels at 1-month post injury. Loss of lamin B1 expression, characteristic of early senescence activation, also was observed in the model 24 hours post burn (P < .01). Matrix metalloproteinase mRNA expression was upregulated early post burn and stayed elevated for up to 4 months post burn compared with nonburn controls.

Conclusions. These data indicate early activation of SASP contributes to the development and maintenance of hypertrophic scars post burn.

Citation: Ayadi AE, Prasai A, Jay J, Wang Y, Herndon D, Finnerty C. Temporal activation of senescence-associated secretory proteins in a post burn hypertrophic scarring model. Poster presented at: Symposium on Advanced Wound Care Spring; May 7-11, 2019; San Antonio, TX.

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This abstract was not subject to the WOUNDS^® peer-review process.

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