{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:35:03Z","timestamp":1791196503895,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,3,12]],"date-time":"2004-03-12T00:00:00Z","timestamp":1079049600000},"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":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The structural rearrangement of collagen fibres in hypertrophic scar causes abnormal contracture, low tensile strength, and raised scars, which cause functional impairment and disfigurement. It is hypothesized that changes in the genes of cytokines, extracellular matrix proteins, and proteins regulating programmed cell death are related to hypertrophic scar formation. To test this hypothesis, fibroblasts were cultured from hypertrophic scars and their response to interleukin\u20106 (IL\u20106) stimulation was studied by defining their gene expression profiles. Affymetrix gene chip analysis was used to identify up\u2010 or down\u2010regulation in the 12 625 genes present in the affymetrix array. RT\u2010PCR and ELISA assays were used to validate microarray expression profiles further. Comparison of gene profiles showed an increase of 12 genes in hypertrophic scar fibroblasts compared with normal skin fibroblasts, while the expression of 14 genes decreased. Thirty\u2010three genes were affected by IL\u20106 treatment in the hypertrophic scar fibroblasts, while 57 genes were affected in normal skin fibroblasts. Messenger RNA to \u03b2\u2010actin ratios for matrix metalloproteinase\u20101 (MMP\u20101) and MMP\u20103 were increased with IL\u20106 in normal skin fibroblasts from 2.43 \u00b1 0.06 to 5.50 \u00b1 0.45 and from 0.75 \u00b1 0.09 to 1.98 \u00b1 0.01, respectively. No change in these matrix metalloproteinases could be shown with IL\u20106 stimulation in hypertrophic scar fibroblasts. Secreted protein levels of pro\u2010MMP\u20101 and MMP\u20103 were elevated in the supernatants from normal skin fibroblasts from 2.00 \u00b1 0.09 and 1.72 \u00b1 0.10 ng\/ml to 4.60 \u00b1 0.12 and 3.41 \u00b1 0.20 ng\/ml, respectively, after treatment with IL\u20106 (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). No changes were observed in hypertrophic scar fibroblasts treated with IL\u20106. Values are means \u00b1 SEM. The absence of any up\u2010regulation of MMP\u20101 and MMP\u20103 in hypertrophic scar fibroblasts, in response to IL\u20106, suggests that suppression of matrix metalloproteinases may play a role in the excessive accumulation of collagen formed in hypertrophic scars. While the pathogenesis of abnormal hypertrophic scars remains poorly understood, the use of gene expression arrays may prove helpful in identifying the mechanisms responsible for this type of abnormal scar formation and in formulating an effective therapeutic protocol. Copyright \u00a9 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.1539","type":"journal-article","created":{"date-parts":[[2004,4,7]],"date-time":"2004-04-07T03:28:46Z","timestamp":1081308526000},"page":"476-485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Gene expression profiles from hypertrophic scar fibroblasts before and after IL\u20106 stimulation"],"prefix":"10.1002","volume":"202","author":[{"given":"Mohan RK","family":"Dasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hal K","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E","family":"Barrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N","family":"Herndon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,3,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0900417"},{"key":"e_1_2_6_3_2","first-page":"275","volume-title":"The Molecular and Cellular Biology of Wound Repair","author":"Roberts A","year":"1996"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.105.2.965"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.1.251"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12627386"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004630-200021020-00010"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00170.2002"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/rp.58.1.75"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.31"},{"key":"e_1_2_6_12_2","unstructured":"DudoitS YangYH CallowM SpeedTP.Statistical methods for identifying differentially expressed genesin replicated cDNA microarray experiments.Technical Report #578. 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