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Elevated lactate levels, increased oxidative stress and myofibroblast formation have all been previously reported. In the current study, we assess the role of Quercetin on collagen secretion and myofibroblast formation in KC <jats:italic>in vitro<\/jats:italic>. Human corneal fibroblasts(HCFs) and human keratoconus cells(HKCs) were treated with a stable Vitamin C derivative and cultured for 4 weeks, stimulating formation of a self-assembled extracellular matrix. All samples were analyzed using Western blots and targeted tandem mass spectrometry. Our data showed that Quercetin significantly down regulates myofibroblast differentiation and fibrotic markers, such as \u03b1-smooth muscle actin (\u03b1-SMA) and Collagen III (Col III), in both HCFs and HKCs. Collagen III secretion was reduced 80% in both HCFs and HKCs following Quercetin treatment. Furthermore, Quercetin reduced lactate production by HKCs to normal HCF levels. Quercetin down regulated TGF-\u03b2R2 and TGF-\u03b22 expression in HKCs suggesting a significant link to the TGF-\u03b2 pathway. These results assert that Quercetin is a key regulator of fibrotic markers and ECM assembly by modulating cellular metabolism and TGF-\u03b2 signaling. Our study suggests that Quercetin is a potential therapeutic for treatment of corneal dystrophies, such as KC.<\/jats:p>","DOI":"10.1038\/srep09003","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T10:04:07Z","timestamp":1426068247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus"],"prefix":"10.1038","volume":"5","author":[{"given":"T. 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D.K and T.M have submitted a provisional patent application relating to the use of Quercetin for treating ocular conditions, which has been filed by the Board of Regents of the University of Oklahoma.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9003"}}