{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:20:45Z","timestamp":1789654845148,"version":"4.0.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T00:00:00Z","timestamp":1480464000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T00:00:00Z","timestamp":1480464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including \u03b1-SMA expression and collagen secretion\/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and \u03b1-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring.<\/jats:p>","DOI":"10.1038\/srep37553","type":"journal-article","created":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T10:21:15Z","timestamp":1480501275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation"],"prefix":"10.1038","volume":"6","author":[{"given":"Chong","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuangang","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,30]]},"reference":[{"key":"BFsrep37553_CR1","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nrm809","volume":"3","author":"JJ Tomasek","year":"2002","unstructured":"Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C. & Brown, R. A. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3, 349\u2013363 (2002).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFsrep37553_CR2","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1111\/exd.12419","volume":"23","author":"LJ van den Broek","year":"2014","unstructured":"van den Broek, L. J., Limandjaja, G. C., Niessen, F. B. & Gibbs, S. Human hypertrophic and keloid scar models: principles, limitations and future challenges from a tissue engineering perspective. Exp Dermatol 23, 382\u2013386 (2014).","journal-title":"Exp Dermatol"},{"key":"BFsrep37553_CR3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1517\/14728214.2015.1018176","volume":"20","author":"ER Zielins","year":"2015","unstructured":"Zielins, E. R. et al. Emerging drugs for the treatment of wound healing. Expert Opin Emerg Drugs 20, 235\u2013246 (2015).","journal-title":"Expert Opin Emerg Drugs"},{"key":"BFsrep37553_CR4","doi-asserted-by":"publisher","first-page":"5880","DOI":"10.4081\/dr.2015.5880","volume":"7","author":"CD Jones","year":"2015","unstructured":"Jones, C. D., Guiot, L., Samy, M., Gorman, M. & Tehrani, H. The Use of Chemotherapeutics for the Treatment of Keloid Scars. Dermatol Reports 7, 5880 (2015).","journal-title":"Dermatol Reports"},{"key":"BFsrep37553_CR5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1684\/ejd.2014.2356","volume":"24","author":"S Meaume","year":"2014","unstructured":"Meaume, S., Le Pillouer-Prost, A., Richert, B., Roseeuw, D. & Vadoud, J. Management of scars: updated practical guidelines and use of silicones. Eur J Dermatol 24, 435\u2013443 (2014).","journal-title":"Eur J Dermatol"},{"key":"BFsrep37553_CR6","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1111\/j.1524-475X.2008.00416.x","volume":"16","author":"M Sisco","year":"2008","unstructured":"Sisco, M. et al. Antisense inhibition of connective tissue growth factor (CTGF\/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo. Wound Repair Regen 16, 661\u2013673 (2008).","journal-title":"Wound Repair Regen"},{"key":"BFsrep37553_CR7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.coph.2015.07.005","volume":"24","author":"G McClorey","year":"2015","unstructured":"McClorey, G. & Wood, M. J. An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies. Curr Opin Pharmacol 24, 52\u201358 (2015).","journal-title":"Curr Opin Pharmacol"},{"key":"BFsrep37553_CR8","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1038\/nm.2807","volume":"18","author":"TA Wynn","year":"2012","unstructured":"Wynn, T. A. & Ramalingam, T. R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nature Medicine 18, 1028\u20131040 (2012).","journal-title":"Nature Medicine"},{"key":"BFsrep37553_CR9","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.burns.2005.07.004","volume":"32","author":"T Stipcevic","year":"2006","unstructured":"Stipcevic, T., Piljac, A. & Piljac, G. Enhanced healing of full-thickness burn wounds using di-rhamnolipid. Burns 32, 24\u201334 (2006).","journal-title":"Burns"},{"key":"BFsrep37553_CR10","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jdermsci.2005.08.005","volume":"40","author":"T Stipcevic","year":"2005","unstructured":"Stipcevic, T., Piljac, T. & Isseroff, R. R. Di-rhamnolipid from Pseudomonas aeruginosa displays differential effects on human keratinocyte and fibroblast cultures. J Dermatol Sci 40, 141\u2013143 (2005).","journal-title":"J Dermatol Sci"},{"key":"BFsrep37553_CR11","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1097\/BCR.0b013e3181667557","volume":"29","author":"ML Ramos","year":"2008","unstructured":"Ramos, M. L., Gragnani, A. & Ferreira, L. M. Is there an ideal animal model to study hypertrophic scarring? J Burn Care Res 29, 363\u2013368 (2008).","journal-title":"J Burn Care Res"},{"key":"BFsrep37553_CR12","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1111\/1523-1747.ep12371710","volume":"101","author":"WL Garner","year":"1993","unstructured":"Garner, W. L., Karmiol, S., Rodriguez, J. L., Smith, D. J. Jr. & Phan, S. H. Phenotypic differences in cytokine responsiveness of hypertrophic scar versus normal dermal fibroblasts. J Invest Dermatol 101, 875\u2013879 (1993).","journal-title":"J Invest Dermatol"},{"key":"BFsrep37553_CR13","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1159\/000121335","volume":"81","author":"XL Xu","year":"2008","unstructured":"Xu, X. L. et al. Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes via the sarcoplasmic reticulum Ca-ATPase. Pharmacology 81, 325\u2013332 (2008).","journal-title":"Pharmacology"},{"key":"BFsrep37553_CR14","doi-asserted-by":"publisher","first-page":"10187","DOI":"10.1007\/s00253-014-6065-0","volume":"98","author":"L Jiang","year":"2014","unstructured":"Jiang, L., Shen, C., Long, X., Zhang, G. & Meng, Q. Rhamnolipids elicit the same cytotoxic sensitivity between cancer cell and normal cell by reducing surface tension of culture medium. Appl Microbiol Biotechnol 98, 10187\u201310196 (2014).","journal-title":"Appl Microbiol Biotechnol"},{"key":"BFsrep37553_CR15","doi-asserted-by":"publisher","first-page":"4199","DOI":"10.1167\/iovs.13-13572","volume":"55","author":"L Yang","year":"2014","unstructured":"Yang, L. et al. Inhibition by all-trans-retinoic acid of transforming growth factor-\u03b2-induced collagen gel contraction mediated by human tenon fibroblasts. Investigative Ophthalmology & Visual Science 55, 4199\u20134205 (2014).","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"BFsrep37553_CR16","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/nm.2005","volume":"15","author":"L Hecker","year":"2009","unstructured":"Hecker, L. et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat Med 15, 1077\u20131081 (2009).","journal-title":"Nat Med"},{"key":"BFsrep37553_CR17","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1097\/00006534-199709000-00021","volume":"100","author":"DE Morris","year":"1997","unstructured":"Morris, D. E. et al. Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg 100, 674\u2013681 (1997).","journal-title":"Plast Reconstr Surg"},{"key":"BFsrep37553_CR18","doi-asserted-by":"publisher","first-page":"e112274","DOI":"10.1371\/journal.pone.0112274","volume":"9","author":"Q Hou","year":"2014","unstructured":"Hou, Q. et al. The four-herb Chinese medicine ANBP enhances wound healing and inhibits scar formation via bidirectional regulation of transformation growth factor pathway. PLoS One 9, e112274 (2014).","journal-title":"PLoS One"},{"key":"BFsrep37553_CR19","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/scrt526","volume":"5","author":"YL Liu","year":"2014","unstructured":"Liu, Y. L. et al. Mesenchymal stem cell-mediated suppression of hypertrophic scarring is p53 dependent in a rabbit ear model. Stem Cell Res Ther 5, 136 (2014).","journal-title":"Stem Cell Res Ther"},{"key":"BFsrep37553_CR20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1465-9921-15-51","volume":"15","author":"F Luo","year":"2014","unstructured":"Luo, F. et al. Arsenic trioxide inhibits transforming growth factor-beta1-induced fibroblast to myofibroblast differentiation in vitro and bleomycin induced lung fibrosis in vivo. Respir Res 15, 51 (2014).","journal-title":"Respir Res"},{"key":"BFsrep37553_CR21","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1096\/fj.14-256263","volume":"28","author":"AT Reddy","year":"2014","unstructured":"Reddy, A. T., Lakshmi, S. P., Zhang, Y. & Reddy, R. C. Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages. FASEB J 28, 5299\u20135310 (2014).","journal-title":"FASEB J"},{"key":"BFsrep37553_CR22","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.intimp.2014.06.031","volume":"22","author":"CH Lin","year":"2014","unstructured":"Lin, C. H., Shen, M. L., Kao, S. T. & Wu, D. C. The effect of sesamin on airway fibrosis in vitro and in vivo. Int Immunopharmacol 22, 141\u2013150 (2014).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep37553_CR23","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/j.1067-1927.2005.130211.x","volume":"13","author":"L Cuttle","year":"2005","unstructured":"Cuttle, L. et al. Collagen in the scarless fetal skin wound: detection with picrosirius-polarization. Wound Repair Regen 13, 198\u2013204 (2005).","journal-title":"Wound Repair Regen"},{"key":"BFsrep37553_CR24","doi-asserted-by":"publisher","first-page":"e68771","DOI":"10.1371\/journal.pone.0068771","volume":"8","author":"W Cui","year":"2013","unstructured":"Cui, W. et al. Electrospun poly(L-lactide) fiber with ginsenoside rg3 for inhibiting scar hyperplasia of skin. PLoS One 8, e68771 (2013).","journal-title":"PLoS One"},{"key":"BFsrep37553_CR25","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/exd.12665","volume":"24","author":"X Bai","year":"2015","unstructured":"Bai, X. et al. Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-beta\/Smad pathway. Exp Dermatol 24, 355\u2013360 (2015).","journal-title":"Exp Dermatol"},{"key":"BFsrep37553_CR26","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00284-008-9139-3","volume":"56","author":"AV Sotirova","year":"2008","unstructured":"Sotirova, A. V., Spasova, D. I., Galabova, D. N., Karpenko, E. & Shulga, A. Rhamnolipid-biosurfactant permeabilizing effects on gram-positive and gram-negative bacterial strains. Current Microbiology 56, 639\u2013644 (2008).","journal-title":"Current Microbiology"},{"key":"BFsrep37553_CR27","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1111\/j.1699-0463.1989.tb00519.x","volume":"97","author":"A Kharami","year":"1989","unstructured":"Kharami, A., Bibi, Z., Nielsen, H., H\u00f8iby, N. & D\u00f6ring, G. Effect of Pseudomonas aeruginosa rhamnolipid on human neutrophil and monocyte function. APMIS 97, 1068\u20131072 (1989).","journal-title":"APMIS"},{"key":"BFsrep37553_CR28","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/BF01626559","volume":"10","author":"TR Shryock","year":"1984","unstructured":"Shryock, T. R., Silver, S. A., Banschbach, M. W. & Kramer, J. C. Effect of Pseudomonas aeruginosa rhamnolipid on human neutrophil migration. Current Microbiology 10, 323\u2013328 (1984).","journal-title":"Current Microbiology"},{"key":"BFsrep37553_CR29","doi-asserted-by":"publisher","first-page":"18581","DOI":"10.1073\/pnas.0903353106","volume":"106","author":"JY Tinevez","year":"2009","unstructured":"Tinevez, J. Y. et al. Role of cortical tension in bleb growth. Proc Natl Acad Sci USA 106, 18581\u201318586 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep37553_CR30","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1242\/jcs.112.5.719","volume":"112","author":"T Togo","year":"1999","unstructured":"Togo, T., Alderton, J. M., Bi, G. Q. & Steinhardt, R. A. The mechanism of facilitated cell membrane resealing. Journal of Cell Science 112, 719\u2013731 (1999).","journal-title":"Journal of Cell Science"},{"key":"BFsrep37553_CR31","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.chemphyslip.2009.06.145","volume":"161","author":"M Sanchez","year":"2009","unstructured":"Sanchez, M., Aranda, F. J., Teruel, J. A. & Ortiz, A. Interaction of a bacterial dirhamnolipid with phosphatidylcholine membranes: a biophysical study. Chem Phys Lipids 161, 51\u201355 (2009).","journal-title":"Chem Phys Lipids"},{"key":"BFsrep37553_CR32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ijpharm.2006.06.028","volume":"325","author":"A Ortiz","year":"2006","unstructured":"Ortiz, A. et al. Effects of dirhamnolipid on the structural properties of phosphatidylcholine membranes. Int J Pharm 325, 99\u2013107 (2006).","journal-title":"Int J Pharm"},{"key":"BFsrep37553_CR33","doi-asserted-by":"publisher","first-page":"142","DOI":"10.2310\/7750.2008.07052","volume":"12","author":"A Piljac","year":"2008","unstructured":"Piljac, A., Stipcevic, T., Piljac-Zegarac, J. & Piljac, G. Successful treatment of chronic decubitus ulcer with 0.1% dirhamnolipid ointment. J Cutan Med Surg 12, 142\u2013146 (2008).","journal-title":"J Cutan Med Surg"},{"key":"BFsrep37553_CR34","unstructured":"Reilly, S. K., Hollis, L., Jones, R. S. & Greenway, D. Biopesticides registration action document-Rhamnolipid biosurfactant (PC Code 110029). US Environmental Protection Agency Office of Pesticide Programs (2009)."},{"key":"BFsrep37553_CR35","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.tifs.2007.01.002","volume":"18","author":"M Nitschke","year":"2007","unstructured":"Nitschke, M. & Costa, S. G. V. A. O. Biosurfactants in food industry. Trends in Food Science & Technology 18, 252\u2013259 (2007).","journal-title":"Trends in Food Science & Technology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep37553.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37553","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37553.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:22:25Z","timestamp":1672885345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep37553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,30]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep37553"],"URL":"https:\/\/doi.org\/10.1038\/srep37553","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,30]]},"assertion":[{"value":"1 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37553"}}