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In addition to proliferation, several cellular stress conditions, such as hypoxia, in the wound micro\u2010environment lead to the accumulation of unfolded or misfolded proteins in the ER, causing ER stress. Eukaryotic cells have a signalling system to manage ER stress called the unfolded protein response (UPR). Mild UPR activation has a beneficial homeostatic effect; however, excessive UPR induces cell death. Herein, we examined venous leg ulcer biopsies versus normal acute incisional wounds in age\u2010matched elderly subjects and found a large increase in ER stress markers. To study the underlying mechanism, we established several cell cultures from amputated legs from the elderly that showed inherent ER stress. While both keratinocytes and fibroblasts migration was impaired by ER stress, migration of elderly leg skin keratinocytes was markedly improved after treatment with the chemical chaperone and clinically established drug 4\u2010phenylbutyrate (4\u2010PBA) and demonstrated a reduction in ER stress markers. In a full\u2010thickness human skin wound healing model, 4\u2010PBA improved the reepithelialisation rate, which suggests it as a promising drug repurposing candidate for wound healing.<\/jats:p>","DOI":"10.1111\/iwj.13525","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T07:59:55Z","timestamp":1606118395000},"page":"49-61","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Endoplasmic reticulum stress in human chronic wound healing: Rescue by 4\u2010phenylbutyrate"],"prefix":"10.1111","volume":"18","author":[{"given":"Etty","family":"Bachar\u2010Wikstrom","sequence":"first","affiliation":[{"name":"Dermatology and Venereology Division Department of Medicine (Solna), Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Manchanda","sequence":"additional","affiliation":[{"name":"Dermatology and Venereology 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