Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

• DOI: 10.1038/ejhg.2017.4
• Publication Date: 2017-02-01T11:23:42Z
• Authors: Michal Kabza; Justyna A Karolak; Malgorzata Rydzanicz; Michał W Szcześniak; Dorota M Nowak; Barbara Ginter-Ma...; Piotr Polakowski; Rafal Ploski; Jacek P Szaflik; Marzena Gajecka
• Keywords: 0301 basic medicine; Down-Regulation; Protein Serine-Threonine Kinases; Keratoconus; Cornea; 03 medical and health sciences; Transforming Growth Factor beta; Case-Control Studies; Humans; Hippo Signaling Pathway; Collagen; Transcriptome; Wnt Signaling Pathway

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.