title: Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.
abstract: To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Department of Bioinformatics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, Poznan, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Kabza
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Karolak
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Bioinformatics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, Poznan, Poland.
authors.forename: Michał W
authors.initials: MW
authors.lastname: Szcześniak
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Nowak
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Barbara
authors.identifier: 0000-0003-4516-1409
authors.initials: B
authors.lastname: Ginter-Matuszewska
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Polakowski
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Gajecka
mesh_terms: D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D000090683:Hippo Signaling Pathway; D006801:Humans; D007640:Keratoconus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases