{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:35:06Z","timestamp":1776350106266,"version":"3.51.2"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypertrophic scars (HTS) are a common complication following burn injuries with prolonged inflammation. They do not respond well to current treatment options including mechanical, biomolecular and surgical therapies. Toll\u2010like receptor (TLR) 2 and 4 respond to microbes and damaged endogenous ligands to trigger pro\u2010inflammatory pathways, and they are expressed more in HTS fibroblasts compared to normal skin fibroblasts. TLR2 responds to microbial lipoteichoic acid (LTA) while TLR4 responds to microbial lipopolysaccharide (LPS) and endogenous ligands. We investigated the role of burn tissue and small leucine\u2010rich proteoglycans (decorin and biglycan) in the stimulation of TLR2 and TLR4 pathways using cells stably transfected with TLR2 or TLR4 linked to a reporter system. Normal skin (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) was collected post\u2010abdominoplasty, and burn eschar samples (<jats:italic>n<\/jats:italic>\u00a0=\u00a018) were collected from 18 patients between 0 and 14\u2009days post\u2010burn. We found that burn tissue stimulates TLR2 activity significantly more than normal tissue and contains significantly higher levels of LTA. Burn tissue was a stronger stimulator of TLR4 than was normal skin. Burn tissue samples' stimulation of TLR4 and TLR2 correlated. The time post\u2010burn (0\u201314\u2009days) of wound tissue sampling correlated positively but moderately with TLR2 and TLR4 simulation. In comparison to the dose\u2010dependent effects of natural decorin or biglycan on TLR4 activation, their denatured forms exhibited stronger or weaker stimulation, respectively. They were not potent stimulators of TLR2. TLR2 and TLR4 stimulation is not limited to bacteria in wounds and likely involves multiple endogenous damage\u2010associated molecular patterns. Insight into mechanisms of HTS will facilitate the development of future targeted therapies to modify wound progression and provide benefits to patients suffering with HTS and other fibroproliferative disorders.<\/jats:p>","DOI":"10.1111\/wrr.12940","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T18:19:43Z","timestamp":1622139583000},"page":"810-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Stimulation of toll\u2010like receptor pathways by burn eschar tissue as a possible mechanism for hypertrophic scarring"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-5571","authenticated-orcid":false,"given":"Ambika","family":"Agrawal","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9642-0290","authenticated-orcid":false,"given":"Jie","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babita","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter O.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E.","family":"Tredget","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2017.03.017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hcl.2016.12.004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2017.0733"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cps.2009.05.014"},{"issue":"5","key":"e_1_2_8_6_1","first-page":"154","article-title":"Review of silicone gel sheeting and silicone gel for the prevention of hypertrophic scars and 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