Quercetin attenuates lactate production and extracellular matrix secretion in keratoconus

Scientific Reports
T B McKayD Karamichos

Abstract

Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and the formation of a cone-like cornea. 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 in vitro. 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 α-smooth muscle actin (α-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-βR2 and TGF-β2 expression in HKCs suggesting a significant link to the TGF-β pathway. These results assert that Quercetin is a key regulator of fibrotic markers and ECM assembly by modulating cellular met...Continue Reading

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Citations

Jun 23, 2015·Journal of Functional Biomaterials·Desiree ' LyonDimitrios Karamichos
Jul 16, 2015·Cell Biochemistry and Function·Tina B McKayDimitrios Karamichos
Sep 25, 2016·Progress in Retinal and Eye Research·Xiaowu GuMichael H Elliott
Jan 7, 2017·Experimental Biology and Medicine·Tina B McKay, Dimitrios Karamichos
Feb 18, 2017·Scientific Reports·Tina B McKayDimitrios Karamichos
Feb 12, 2017·Journal of Lipid Research·Hui QiDimitrios Karamichos
Aug 31, 2019·Scientific Reports·Rabab SharifDimitrios Karamichos
Oct 17, 2019·Cells·Tina B McKayDimitrios Karamichos
Sep 26, 2019·Scientific Reports·Amy E WhelchelDimitrios Karamichos
Feb 10, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lianghui ZhaoXianli Du
May 14, 2021·Frontiers in Pharmacology·Md Moklesur Rahman SarkerIsa Naina Mohamed
Jul 3, 2021·European Journal of Ophthalmology·Ruixing Liu, Xiaoming Yan

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Methods Mentioned

BETA
scraping
Protein Assay
electrophoresis

Software Mentioned

Graph Pad Prism
OMEGA Carestream MI Standard
MetaboAnalyst
MultiQuant

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