{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:23:49Z","timestamp":1790227429564,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,3,17]],"date-time":"2005-03-17T00:00:00Z","timestamp":1111017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypertrophic scarring is a pathological process characterized by fibroblastic hyperproliferation and by excessive deposition of extracellular matrix components. It has been hypothesized that abnormalities in epidermal\u2013dermal crosstalk explain this pathology. To test this hypothesis, a tissue\u2010engineered model of self\u2010assembled reconstructed skin was used in this study to mimic interactions between dermal and epidermal cells in normal or pathological skin. These skin equivalents were constructed using three dermal cell types: normal wound (Wmyo) or hypertrophic wound (Hmyo) myofibroblasts and normal skin fibroblasts (Fb). Epidermis was reconstructed with normal skin keratinocytes (NK) or hypertrophic scar keratinocytes (HK). In the absence of keratinocytes, Hmyo formed a thicker dermis than Wmyo. When seeded with NK, the dermal thickness of Hmyo (121.2 \u00b1 31.4 \u00b5m vs 196.2 \u00b1 27.8 \u00b5m) and Fb (43.7 \u00b1 7.1 \u00b5m vs 83.6 \u00b1 16.3 \u00b5m) dermis was significantly (<jats:italic>p<\/jats:italic> &lt; 0.05) reduced, while that of Wmyo (201.5 \u00b1 15.7 \u00b5m vs 160.7 \u00b1 21.1 \u00b5m) was increased. However, the presence of HK always induced significantly thicker dermis formation than observed with NK (Wmyo: 238.8 \u00b1 25.9 \u00b5m; Hmyo: 145.5 \u00b1 22.4 \u00b5m; Fb: 74.2 \u00b1 11.2 \u00b5m). These results correlated with collagen and MMP\u20101 secretion and with cell proliferation, which were increased when keratinocytes were added, except for the collagen secretion of Hmyo and Fb in the presence of NK. The level of dermal apoptosis was not different when epidermis was added to the dermis (&lt;1% in each category). These observations strongly suggest that hypertrophic scar keratinocytes play a role in the development of pathological fibrosis by influencing the behaviour of dermal cells. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1737","type":"journal-article","created":{"date-parts":[[2005,3,17]],"date-time":"2005-03-17T05:46:36Z","timestamp":1111038396000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Epidermis promotes dermal fibrosis: role in the pathogenesis of hypertrophic scars"],"prefix":"10.1002","volume":"206","author":[{"given":"Judith","family":"Bellemare","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J","family":"Roberge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Bergeron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Lopez\u2010Vall\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique J","family":"Moulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02147594"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3827"},{"key":"e_1_2_6_4_2","first-page":"56","article-title":"Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar","volume":"146","author":"Desmouli\u00e8re A","year":"1995","journal-title":"Am J Pathol"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.8.11.8070631"},{"key":"e_1_2_6_6_2","first-page":"16","article-title":"Defining apoptosis","volume":"146","author":"Hockenbery D","year":"1995","journal-title":"Am J Pathol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/24055"},{"key":"e_1_2_6_8_2","first-page":"465","article-title":"Enhanced expression of mRNA for transforming growth factor\u2010b, type I and type III procollagen in human post\u2010burn hypertrophic scar tissues","volume":"122","author":"Ghahary A","year":"1993","journal-title":"J Lab Clin Med"},{"key":"e_1_2_6_9_2","first-page":"105","article-title":"Morphological and immunochemical differences between keloid and hypertrophic scar","volume":"145","author":"Ehrlich HP","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-198310000-00009"},{"key":"e_1_2_6_11_2","first-page":"1133","article-title":"Activated keratinocytes in the epidermis of hypertrophic scars","volume":"152","author":"Machesney M","year":"1998","journal-title":"American Journal of Pathology"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050331"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12371721"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12371732"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-200103000-00022"},{"key":"e_1_2_6_16_2","first-page":"875","article-title":"Interactions keratinocytes\u2010fibroblasts. 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