PMID- 24835866 OWN - NLM STAT- MEDLINE DCOM- 20150105 LR - 20211203 IS - 1536-3708 (Electronic) IS - 0148-7043 (Print) IS - 0148-7043 (Linking) VI - 72 IP - 6 DP - 2014 TI - Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars. PG - 711-9 LID - 10.1097/SAP.0b013e31826956f6 [doi] AB - Excess scar formation after cutaneous injury can result in hypertrophic scar (HTS) or keloid formation. Modern strategies to treat pathologic scarring represent nontargeted approaches that produce suboptimal results. Mammalian target of rapamycin (mTOR), a central mediator of inflammation, has been proposed as a novel target to block fibroproliferation. To examine its mechanism of action, we performed genomewide microarray on human fibroblasts (from normal skin, HTS, and keloid scars) treated with the mTOR inhibitor, rapamycin. Hypertrophic scar and keloid fibroblasts demonstrated overexpression of collagen I and III that was effectively abrogated with rapamycin. Blockade of mTOR specifically impaired fibroblast expression of the collagen biosynthesis genes PLOD, PCOLCE, and P4HA, targets significantly overexpressed in HTS and keloid scars. These data suggest that pathologic scarring can be abrogated via modulation of mTOR pathways in procollagen and collagen processing. FAU - Wong, Victor W AU - Wong VW AD - From the *Division of Plastic and Reconstructive Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR; and daggerDivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University, Stanford, CA. FAU - You, Fanglei AU - You F FAU - Januszyk, Michael AU - Januszyk M FAU - Gurtner, Geoffrey C AU - Gurtner GC FAU - Kuang, Anna A AU - Kuang AA LA - eng GR - T15 LM007033/LM/NLM NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann Plast Surg JT - Annals of plastic surgery JID - 7805336 RN - 0 (Immunosuppressive Agents) RN - 9007-34-5 (Collagen) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adult MH - Aged MH - Cicatrix, Hypertrophic/drug therapy/metabolism MH - Collagen/biosynthesis/metabolism MH - Dose-Response Relationship, Drug MH - Down-Regulation/physiology MH - Female MH - Fibroblasts/*drug effects MH - Humans MH - Immunosuppressive Agents/*pharmacology MH - Keloid/drug therapy/metabolism MH - Male MH - Middle Aged MH - Phosphorylation MH - Protein Array Analysis MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors PMC - PMC4886898 MID - NIHMS775726 EDAT- 2014/05/20 06:00 MHDA- 2015/01/06 06:00 PMCR- 2016/05/31 CRDT- 2014/05/20 06:00 PHST- 2014/05/20 06:00 [entrez] PHST- 2014/05/20 06:00 [pubmed] PHST- 2015/01/06 06:00 [medline] PHST- 2016/05/31 00:00 [pmc-release] AID - 00000637-201406000-00021 [pii] AID - 10.1097/SAP.0b013e31826956f6 [doi] PST - ppublish SO - Ann Plast Surg. 2014;72(6):711-9. doi: 10.1097/SAP.0b013e31826956f6.